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update 7 November 2015: comments & feedback please.Orthoiodosupplementation in a Primary Care PracticeJorge D. Flechas, M.D. its undatedbut the latest ref is 2004..
but informative 2014 iodine update video by Dr Jorge Flechas:
some points: “why women have so many more thyroid problems eg estrogen blocks iodine; whereas ovary hot nodules may cause thyrotoxicosis from secreting T2. Iodine alerts the brain, so dont take at night! give no more than ~12mg/d ie 2 drops 15% in pregnancy, it stimulates the baby!“Iodine ie I2 diffuses into cells whereas iodide need to be transported in; babies lack the symporter Iodide transporter, so babies need iodine not iodide.ie thyroid, ovary and WBCs can make thyroxine- but preferably they mop up low iodine intake. Thyroid supplements doesnt provide enough iodine for needs elsewhere . ” Millions of women in Japan and Korea on their marine diet used to normally ingest ~13.5mg iodine a day, producing very low neonate problem rates in pregnancy and with IQ far higher than average.“in the west, Iodine has been taken out of bread and milk, and salt intake cut – associated with increased rate of ADD in USA 500% and more cancer thyroid, breast, ovaries, endomet, cretinism, goitre .. – as iodine intake and output in USA has been halved by admin policy… the kidneys excrete excess ingested iodine, so avoiding overdose from high iodine intake.

“ie if sufficiency, a 50mg iodine load will excrete >90% . so the spot test for low iodine excretion, and 24 hr high iodine excretion, reflect defective sodium symporter problem. This corrects with ongoing iodine supplement. 80% of vegans in USA are iodine deficient due to skipping seaweed for iodine! Asians eat seaweed in everything.. the body can hold 1.5gms iodine; 50mg in the thyroid, 20% in the skin, 30% in muscles… – if depleted of iodine, we cant sweat or use our muscles (fibromyalgia), brains, or control the breasts or ovaries.. .. just add ATP cofactor ie incl vits B2 & B3 to iodine… “Bread & esp cooldrink’ iodine (eg Mountain Dew) has been replaced by bromine, which causes schizoid behaviour… .. Iodine reverses the immortality of cancer cells. ” 3000mg/d ester C , and highdose iodine, and B2+B3 , reverse the iodine symporter block, & abolish the fibromyalgia in 80% of sufferers. .

It does seem that as with vits C and D3, iodine has a minimal RDA as far as basic prevention goes ie ~0.15mg – 1mg/d for avoiding cretinism (cf scurvy with >10mg/d vit C, or frank rickets with 400iu/d vit D3) ; and at the other end of the spectrum ie treating severe disease, grams a day of iodine and vit C, and vit D3 >50 000iu ie >1mg/day..

perhaps the corollary may be that , (as with vit D3 eg 2million ie ~ 50mg), a massive accidental load dose eg 2gms iodine- 20ml 15% Lugols- (which apparently bypasses the detox reaction at lower ie buildup dose, and incidentally provides 1gm potassium) may be both harmless and will reload for who knows how many years- presumably provided one takes a good magnesium andselenium ie realfood Banting diet .

To test tolerance, and try to reverse my familial irreversible atrial fibrillation, I have built up my Lugols’ dose so far to 15% 1 to 2 tsp a day ie 4 to 8ml, ~800mg combined (I + I2) iodine with 400mg potassium K a day;
whereas a load dose vit D3 eg 0.6 to a million units (6-10gms of standard max strength 100 cwt powder – with a good magnesium and vit K2 diet as in realfood Banting) will replete safely and harmlessly for less than a year.
Its a pity the simple IODINE urine test is- unlike the skin patch test duration- so tediously long and costly (and both can occasionally mislead),
whereas the blood vit D calcium-creat levels are quick to take but costly tests.. .

But in those who can afford them , the tests are essential to validate the clinical results we get with iodine and vit D3 .

update 27 Sept 2015IODINE THE QUINTESSENTIAL SUPPLEMENT

quotes from authorities are in italics: please feed back on errors and experience

Massive iodine deficiency is as universal worldwide (compared to 50 years ago) as are*deficiencies of: ..vitamin C (except those who live on fresh fruit and veg);
..vitamin D (except those who work outdoors in sunny climes);
..magnesium; and
..natural saturated fats in all except keen carnivores;
..and increasing deficiency of other vitamins in the food chain, forced on the public by government-sponsored industries and “health authorities” for 50 years now;*and unnecessary dangerous food-chain toxins ( refined carbohydrates; calcium/bromine/ fluorine/salt, aluminium, mercury supplements, synthetics eg transfats, pesticides eg glyphos Roundup, GMO foodstuffs, antibiotics ; and steroids). .

But with seafood almost wiped out by greed and pollution, and increasing global nuclear pollution, and failure by food producers to supplement iodine never mind vit D and magnesium in the depleted food chain,

iodine repletion with vigorous Lugols iodine(with its consort selenium) is even more of a priority than concomitant vitamin D (with its consort vit K2) and magnesium supplementation, and vitamin C, plus a broad balanced other score A to Z multisupplement ..

So the dangerous scaremongering myths need to be debunked about the “dangers” of iodine at over a mg a day – when the safe general therapeutic dose is not just ~12mg/d but up to 100mg/d for longterm prevention, and over a gm/d for major diseases; ie >10 000 x the RDA. The US recommended adult dose of iodine for nuclear exposure is about 120mg, without any mention of remotest risk of toxicity.

This 1000 x order of magnitude with iodine is like
*the almost 10 000x margin between minimalistic vitamin C 10mg/d dose (RDA now 60mg/d) to avoid scurvy, up to >3v-7gm a day to treat infections, and >30 gm/day (intravenously, or buffered orally) to treat cancer;

*and vitamin D3 (RDA now up to ~800iu/d) up to 250 x more eg from 200iu /d to prevent rickets vs 50 000iu/d to treat some serious diseases, vs 2million iu single doses and 150 000iu/d for decades that have no documentable toxic effects in adults.
Infants obviously need proportionate dosing of all, not left to depend on mother’s milk when she has received no more than the usual prenatal supp folate and iron.. . .

The heaviest essential metal iodine is perhaps the most rare essential mineral – Wiki: “Iodine is rare in the Solar System and Earth’s crust (47th/60th in abundance):”- hence iodine deficiency is universal – especially now it has become fashionable in our lifetime to stop adding iodine to foodstuffs; and instead food manufacturers pump in toxic halides like bromine and fluoride (like dangerous mercury and aluminium in vaccines, aluminium in antacids) that (unlike chlorine, iodine and refined sugars) have no essential biological need and benefit , only risks;

and recognition that commercial pure white runny salt NaCl – overdosing chlorine- is adverse because of worsening hypertension with aging and fast foods, instead of encouraging seasalt. .The myths have been debunked that
*(unlike our essential blood chlorine in moderation), either fluorine or bromine are essential trace element halogens, any more than commercial cane sugar or fructose are biologically essential in our diet;

*and the Wolff-ChaikoffEffect myths (that iodine is toxic at much more than a mg a day) debunked by Abraham & Brownstein’s reviewof scientific evidence the past century including Wartofsky, et al 1970 that we overdose with iodine at only 20 x the RDA (0.15mg/d) ie over a mg/ day,

*and the myth that only potass KI /sodium NaI iodides should be supplemented. The most proven iodine is in Lugols iodide providing the balance between KI and free I2.

*Another commercially driven myth is that blood thyroid hormone levels are adequate to diagnose biologically significant iodine sufficiency, and commercial thyroxine to treat patients– the commercial hormones dont address, may worsen the serious iodine deficiency throughout the body that contributes hugely to acute and chronic, common and rare diseases

Studies of traditional Japanese after WW2 showed that their far better cancer-, cardiovascular,- thyroid health (before they emigrated to America, or took up Western diet) was attributable especially to the kelp ie iodine intake in their then-safe seafood diet, giving them an average iodine intake of about 12 mg/day- at least 100 times the current American imposed RDA of 0.15mg/d. But who can trust kelp, seafood from the poisoned oceans and rivers any more?

I recently took for a day each approx 20drops Lugols 2% pd in water ie iodine ~9mg a day; then 15% 4 drops ie 30mg/d …then up to , then 10drops ~70mg/d to test for detox reaction. I carry on with ~50mg/d, as many patients take it . I suppose my lack of detox reaction is not surprising since I have been detoxing for years on about 6 gm a day of a 50 -supp -multiblend( half vit C).- but no more than a mg/d of potass iodide. I find physical and mental stamina better, no longer have angina from stress or walking fast- which I could not do a fortnight before due to angina and fatigue. . .

One shudders to think of the billions of people – especially kids- who are dull, not achieving their full potential for lack of iodine, either because health professionals dont think we need more, or because patients are dismissed as euthyroid based on the usual thyroid lab hormone tests (which ignore iodine deficiency/excess in the majority who dont fall clearly in the over-or underactive blood hormone range).

Conventional western medicine apparently no longer considers or measures iodine deficiency, forgetting that iodine is the primary essential deficient mineral (along with magnesium, selenium, sulphur, phosphate; and iron in kids and reproductive women) for all systems in the body, not just for thyroid hormone levels- which dont reflect iodine security anywhere outside thyroid hormone production by the thyroid. .

IODINE OVERDOSE?Iodine is needed in microgram mcg amounts for the thyroid, milligram mg amounts for breast and other tissues, and therapeutically as anticancer in gram amounts.[2]- Dr. David Miller
The theoretical iodine lethal LD50 for humans ie 1/10th of rodent dose is about 2 gm / kg, eg 6gm for a newborn baby, 140gm for an adult… a bottle of 20ml 2% Lugols in water contains 400mg, a 100ml bottle of 15% in water contains 15gm iodine(ie a 20ml bottle 3g) ie a harmless dose except corrosive if swallowed neat,.

Hence retailers if at all dispense Lugols 2%; we dont lightly prescribe/dispense 15% Lugols except for topical massage. And for cancer and we stick to 20ml dropper bottles.
not even Dischem and Clicks at Cavendish stock Lugols- only 2% iodine tinct IN ALCOHOL ie strictly for burning scratches… so no retailer should sell 100ml of any Lugols prep, only 20ml 2% Lugols, as is enforced in USA. It is indeed apparently regulated in the same way here., ‘tho’ the SA Medicines formulary doesnt mention that (recommends it only preop for eg thyroid storm), nor the multidisease benefits of Lugols including on the brain, wounds, infections, cardiac, vascular, cancer lungs etc;

In perspective, the thyroid holds 50 milligrams of iodine, the breasts hold 200 milligrams, the skin holds 400 milligrams of iodine, and the whole body holds 2,000 milligrams, and possibly much more. Iodine is found and used in every hormonal receptor in the body. in 1911, 900 milligrams 0.9gm/day!) were considered usual and safe dosage. At 6 grams 6,000 milligrams/day!), iodine has been used to cure syphilis, skin lesions, and chronic lung disease. Iodine makes us smarter, helps with mental functioning. Low iodine is associated with low IQ’s with a difference of up to 13.5 points in children; but iodine deficiency is also associated with mental functioning in adults, because iodine not only chelates lead, but, according to Dr. Jorge Flechas, iodine prevents lead from lodging in the body in the first place. Low thyroid function decreases brain circulation, which slows intellectual function. low thyroid function is associated with cognitive impairment, memory loss, depression, slowness of mind, anxiety, suicidal tendencies, and a variety of psychiatric disorders. Bleichrod’s meta-analysis of 17 studies showed iodine sufficiency increases IQ by 13.5 points in children. Iodine prevents heart disease. Iodine is needed with the use of cordless phones, cell phones and now smart meters to prevent hypothyroidism. Iodine decreases insulin needs in diabetics.

IODINE ALLERGY? The risk of iodine allergy is quite low – Drs. Abraham and Brownstein were only able to identify 3 of 4,000 people who had a negative response to the iodine. People do not become allergic to iodine per se, but people react to the displacement of bound heavy metals; and can become allergic to protein-bound iodine as is found in shellfish or to the binding agents, excipients, fillers, preservatives and/or synthetics (rather than the bioavailable form of iodine itself) commonly found in tablets, capsules, and even liquids. Actually, iodine can help eliminate food allergies according to Dr. Derry.But dont take Lugols at the same time as vit C, which neutralizes the antimicrobial effects of Lugols. so take them at opposite ends of the day.

and because iodine attacks only pathogens and abnormal cells, not our good probiotic biomeor healthy cells, it has none of the risks of pesticides , antibiotics, antivirals, radiotherapy, chemotherapy etc.

RESEARCH ON LUGOL’S IODINE?
despite Dr Jean Lugol having published his landmark 1829 work on his iodine complex ie ~185 years ago, there is predictably little research on it published on Pubmed, for the obvious reason that Big Pharma and the Disease Industry and governments wont fund research on such a cheap cure, which would greatly increase survival, but in the short term reduce illness and thus need for health industry workers, hospital beds, pharmacies and new drugs.There are apparently only three clinically relevant LUGOL’s papers listed on Pubmed ie in the past 50 years:-

from India2012 Consul ea– confirming that painting the cervix with Lugols (the Schiller test ) and vinegar is as effective as Pap smear for screening; thus combined, the two simple cancer diagnostic paints make up for Lugols iodine for cervix cancer being only about 85% sensitive and specific ie not as reliable alone as a costly lab Pap smear…Greece 2007 Theodoropoulou ea confirming that preoperative Lugol’s iodine 80mg/d for 15 days in euthyroid people was accompanied by increased intrathyroid total iodine but no changes in intrathyroid hormone HI or demonstrable increases of serum T4 and T3 were observed. It is hypothesized that the maintenance of normal intrathyroidal HI is the result of the combined inhibitory effect of iodine on thyroid hormone synthesis and on the release of T4 and T3 from the thyroid.
andItaly 1986 Maraniea –Iodine is therapeutic in various pathologies where immunity plays a dominant role, eg it facilitates cure in tuberculosis, lepromatous, syphilitic and mycotic incl sporotrichosis lesions . This effect does not depend on iodine’s action on the micro-organism responsible, but on host immune boosting. . Iodine may also be used in Panniculitis, in erythema nodosum, in nodular vasculitis, erythema multiforme etc. . To establish relationship between dietary iodine and immune response, 607 infants in an area of endemic goitre were studied: 215 were given Lugol solution (2 drops- presumably 20mg? a week for about 8 months ; and 392 not. Immune response was assessed by the skin test tetanus toxoid (in the U.S. 80% of paediatric cases aged 2-10 years old were positive). A significant difference was noted in the average diameter of the infiltrations after the tetanus toxoid skin test in the two groups considered (P less than 0.001). The results indicate that an adequate iodine intake is necessary for normal retarded immune response – a fact that the disease industry and Big Pharma blatantly ignore. . . (Iodine does not have the adverse effect of antibiotics on our gut biome, or causing antibiotic-resistant pathogens)

But there are dozens of scientific Lugol’s studies not referenced by Pubmed:

The End of Antibiotics and the Rise of Iodine as an Effective Alternative2008 Mark Sircus

Mamo & NaissidesInternational Journal of Infectious Diseases (2005) from Australia showIodine Could be effective in the treatment of human immunodeficiency virus and AIDS-associated opportunistic infections. as it is in rodents and cats .

Inactivation of human immunodeficiency virus by iodine-releasing productsHarbison & Hammer Boston, Massachusetts 1989 showed that “povidine-iodine completely inactivated HIV at concentrations of greater than or equal to 0.5% ie is highly effective at killing HIV.Betadine is simply “a stable complex of povidone and elemental iodine, contains 9.0% to 12.0% available iodine ie 90-120mg/ml .. Free iodine slowly liberated from the povidone-iodine PVPI solution kills microbe (but not healthy mammalian) cells through iodination of lipids and oxidation of cytoplasmic and membrane compounds, thus exhibits a broad range of microbicidal activity against bacteria fungi protozoa and viruses. Slow release of iodine from the PVPI complex in solution minimizes iodine toxicity towards mammal cells.” This compares exactly with a similar iodine complex 15% Lugols which contains about 10% ie 100mg iodine /ml water .. at far lower cost than but identical safety and efficacy to the patented Betadine – a modern designer marketable patented crib of Lugol’s .. …

Iodine: Its Role In Health and Disease: New Exciting ConceptsMichael B. Schachter, M.D. 2007:Guy Abraham MD, former professor of obsts gyne & endocrinology at UCLA School of Medicine, has written papers about iodine that drastically changed my thinking about its role in health and the prevention and treatment of disease. I had been impressed by Dr. Abraham’s previous work, which showed that vitamin B6 and magnesium could be very helpful to women with premenstrual syndrome (PMS) and was eager to learn what he had to say about iodine. Through a series of articles termed “The Iodine Project,” Dr. Abraham proposed that the optimal daily dose of iodine for a WELL person is approximately 12.5 mg, which is 100 times the RDA of 0.125 mg, ie that the current prevailing medical opinion that more than 2 mg a day of iodine is toxic is wrong. He traces the source of this major blunder to a scientific experiment on rats that was published in 1948 by Drs. Wolff and Chaikoff, which erroneously concluded that iodine inhibits the thyroid gland at doses of about 20 times the recommended daily allowance (RDA) for iodine. This conclusion was later generalized to humans and can be found in medical textbooks, including endocrinology and nutrition textbooks. Guy Abraham wrote in 2005: In hypertension, iodine sufficiency resulted in normalization of blood pressure without medications; as reported by other physicians using this program. Best results were achieved when orthoiodosupplementation was combined with a complete nutritional program emphasizing magnesium instead of calcium. Obesity increases the requirement for iodine and up to 100 mg elemental iodine/day may be required to achieve and maintain sufficiency. Increased demand for iodine occurs with excessive amounts of goitrogens from the diet and lifestyle. eg, smoking increases serum thiocyanate levels, interfering with the sodium/iodide supporter function. Low thyroid iodine is associated with thyroid hyperplasia and cancer. Could thyroid hormones cause the same iodine depletion in breast tissue? The prevalence of breast cancer is higher in women on thyroid hormones. Medical iodophobia resulted in removal of iodate from bread 20 years ago, replacing it with the goitrogen bromate- which associated with increased obesity, diabetes, and hypertension, thyroid and breast cancer. Recent reports show association between low iodine intake in women during pregnancy and attention deficit and hyperactivity disorder (ADHD) in their offspring. The most plausible explanation is a decreased sensitivity of the nuclear thyroid hormone receptor to thyroid hormones. We previously reported evidence for improved receptor response to thyroid hormones following iodosupplementation. Therefore, iodine is not only necessary for the synthesis of thyroid hormones but also for their effect on target cells. This effect is probably due to iodination of the thyroid hormone receptor. The essential element iodine, which is the inorganic, non-radioactive forms, deserves more attention from researchers and clinicians. It maybe the missing link in patients currently resistant to conventional hormonal therapy.
and seehttp://www.earthclinic.com/remedies/lugols-iodine-supplements2.html
re adding enough selenium, chromium, vit C, Magnesium, Vitamin B2/3
and

Until 2007, in the United States, Lugol’s solution was unregulated and available over the counter as a general reagent, an antiseptic, a preservative,[11] or as a medicament for human or veterinary application .

However, effective August 1, 2007, the DEA now regulates Lugol’s solution (and, in fact, all iodine solutions containing greater than 2.2% iodine) as a List I precursor because it may potentially be used in the illicit production of methamphetamine.[12] However, transactions of up to one fluid ounce (30 ml) of Lugol’s solution are exempt from this regulation. When buying Lugol’s Solution on places like Amazon, most sellers fail to indicate the DEA tracking requirement. On the other hand Lugol’s Iodine solution is available over the counter in Canada and Mexico. Toxicity Because it contains free iodine, Lugol’s solution at 2% or 5% concentration without dilution is irritating and destructive to mucosa, such as the lining of the esophagus and stomach.Doses of 10 mL of 5% solution have been reported to cause gastric lesions when used in endoscopy.[13] The LD50 for Iodine is 14,000 mg/kg [Rat] and 22,000 mg/kg [Mouse].[14]Most guidelines accept that anything with an LD50 >2 g/kg (-5 g/kg in some countries) can be classed as having a low acute toxicity[citation needed] which classifies Iodine as having low toxicity. Potassium Iodide is not considered hazardous.[15http://jeffreydachmd.com/breast-cancer-prevention-with-iodine/

Iodine DosagesTreatment of Influenza and other Diseasesiodine-dosages 2009 “After testing over 500 patients, I found that 94.7% of my patients are deficient in inorganic iodine. Dr. David Brownstein In this chapter I will present different views and practices from present as well as from the long past when iodine was vastly more popular as a medicine than it is today. For whatever irrational reason, doctors and patients fear iodine thus en mass do not use to its fullest potential. Humans tolerate large doses of iodine but the ultra high doses that were used many decades ago are not required to get the most out of iodine therapy. Just a little goes a long way, as the governmental iodized salt programs showed but this dosage level was only effective for Goiter and its avoidance. It actually takes very little iodine to prevent this disease but no one ever said that was the only purpose and need for iodine in the body. Today people are more deficient then ever before because our need for iodine has increased in direct proportion to our toxic burdens especially of other competing halogens. Read on at http://drsircus.com/medicine/iodine/iodine-dosages
Pps
see lugols_dosage_chart. . But for obvious reasons stick to 2% till you know you tolerate and need much stronger drops.

More Canadian and USA studies confirm that vigorous vitamin D need applies especially to those living in far northern USA-Canada and EurAsia etc; but also to all of us globally who spend little time well exposed to the sun- especially the more driven who both live/work indoors and cover even our limbs and heads outdoors as eg more ‘observant’ adults of many faiths do. As a new Creighton Univ study shows, we are at minimal risk of kidney stones on vigorous supplement vit D3 provided we balance it with enough water and magnesium supplement,

This is why in this age of increasing stress, longevity, epidemics, and pollution of both environment and the food and medicine chains, we have for a couple of years now been advocating and taking vitamin D3 – on a century of voluminous evidence (62500 papers on Pubmed alone) since 1914 from top nutritional scientists like Drs Jack Drummond, Linus Pauling, Walter Stumpf, Chris Nordin, Chris Gallagher, Rob Heaney, John Cannell, Bill Grant, Mike Holick, Cedric Garland, ea – at least vit D3 50 000iu a week (~7000iu/d) ie a million units every 20 weeks; retail costing R30 ie R6pm for us aging frailer types (half that dose ie 50 000iu twice a month @R3/month for the poor/ well or small kids).. at R12/US$, that costs all of $3 to $6 a year.

On about 9000iu vit D3 average supplement/day, my total 25OH vit D bloodlevel runs about 90-100 ng/ml ie 220-250 nmol/l. so only 400- 1000iu vit D /day will boost the vit D bloodlevel and benefits little if not trivially.

But vigorous D3 dose must be buffered by vit K2 about >100mcg/day , magnesium about 400mg/d, and the usual basket of other ~50 vits, minerals and other natural supplements, to protect us from kidney and arterial calcification etc. We have previously highlighted trials eg from Pakistan showing that even 600 000iu vit D3 a month ie ~20 000iu/day safely and greatly improves recovery and healing from severe PTB+- AIDS in eg frail Pakistatin patients; whereas overdose of 90year old patients with a 2million iu vit D3 dose (in Netherlands) produced no toxicity. Hence we load sick patients with (an antibiotic-like ) 200 000 to 400 000iu dose before continuing weekly or fortnightly maintenance- with the sickest fattest getting the highest dose, and infants scaled down accordingly (after a loading dose of eg 25 000iu) to eg 1000-2000iu/d, or 50000iu 1/2 scoop ie 25000iu every 2 weeks- the older extrapolation (as for adults) of ~100iu/kg/day.

For the concerned vegan, vitamin D is vegetarian: supplement of vit D2 is extracted from yeast or mushrooms; vit D3 by UV irradiation of cholesterol from lanolin. Like all life, since vitamin D soltriol is a sun-induced sterol oil product (in this case of cholesterol which in turn is built via vitamin C ascorbic acid from plant glucose-sugar), vitamin D does not contain or be made from animal flesh ie animal protein nitrogen any more than does fish oil.

Vitamin D may keep low-grade cancer from becoming aggressive: http://www.sciencedaily.com/releases/2015/03/150322080155.htmTaking vitamin D supplements could slow or even reverse the progression of less aggressive, or low-grade, prostate tumors without the need for surgery or radiation, scientists say. Taking vigorous vits C & D does this for all cancers, all disease.

A Statistical Error in the Estimation of the Recommended Dietary Allowance for Vitamin D. Letter to Veugelers, P.J. and Ekwaru, J.P., Nutrients. 2015 Mar 10;7(3):1688-90. doi: 10.3390/nu7031688. Nutrients 2014, 6, 4472-4475; doi:10.3390/nu6104472. Heaney , Garland ea. 1Creighton University & University of California, San Diego,GrassrootsHealth, Encinitas, CA . Recently Veugelers and Ekwaru published data indicating that, in its dietary reference intakes for calcium and vitamin D, the Institute of Medicine (IOM) had made a serious calculation underestimation [2]. Using the same data set as had the IOM panel, these investigators showed that the Recommended Dietary Allowance (RDA) for vitamin D had been underestimated by an order of magnitude. Veugelers and Ekwaru, using the IOM’s data, calculated an RDA of 8895 IU per day. They noted that there was some uncertainty in that estimate, inasmuch as this value required an extrapolation from the available data, which did not include individuals receiving daily vitamin D inputs above 2400 IU/day.[…].

The Institute of Medicine (IOM) issues dietary recommendations on the request of the U.S. and Canadian governments. One of these recommendations is the Recommended Dietary Allowance (RDA). The RDA is the nutrient intake considered to be sufficient to meet the requirements of 97.5% of healthy individuals [1]. The RDA for vitamin D is 600 IU per day for individuals 1 to 70 years of age and is assumed to achieve serum 25-hydroxyvitamin D (25(OH)D) levels of 50 nmol/L or more in 97.5% of healthy individuals [1]. Serum 25(OH)D is the established proxy for vitamin D status and levels of 50 nmol/L or more have been shown to benefit bone health and to prevent disease and injury [1].

The IOM based their RDA for vitamin D on an aggregation of 10 supplementation studies that were carried out during winter months and at locations with latitudes above the 50th parallel north to minimize the influence of cutaneous vitamin D synthesis [2,3,4,5,6,7,8,9,10,11]. As several of these 10 studies examined more than one supplementation dose, collectively they provided 32 study averages of serum 25(OH)D levels. These are replicated as the green diamonds in Figure 1. The IOM regressed the 32 study averages against vitamin D intake to yield the dose response relationship of vitamin D intake and serum 25(OH)D (green solid line in Figure 1). The IOM further calculated the lower and upper 95% confidence prediction interval based on the 32 study averages and the standard deviation of these 32 study averages (green dashed lines in Figure 1). On the basis of this, the IOM estimated that 600 IU of vitamin D would achieve an average 25(OH)D level of 63 nmol/L and a lower 95% confidence prediction limit (2.5 percentile) of 56 nmol/L. The latter value was rounded downwards to 50 nmol/L to accommodate uncertainty in the estimation [1]. This data point (600 IU vitamin D, 50 nmol/L) is the basis for the current RDA and for the IOM’s conclusion that an intake of 600 IU of vitamin D per day will achieve serum 25(OH)D levels of 50 nmol/L or more in 97.5% of individuals.

The correct interpretation of the lower prediction limit is that 97.5% of study averages are predicted to have values exceeding this limit. This is essentially different from the IOM’s conclusion that 97.5% of individuals will have values exceeding the lower prediction limit. To illustrate the difference between the former and latter interpretation, we estimated how much vitamin D is needed to achieve that 97.5% of individuals achieve serum 25(OH)D values of 50 nmol/L or more. For this purpose we reviewed each of the 10 studies used by the IOM. Eight studies reported both the average and standard deviation [2,5,6,7,8,9,10,11]. These eight studies had examined a total of 23 supplementation doses [2,5,6,7,8,9,10,11]. For each of these 23 study averages we calculated the 2.5th percentile by subtracting 2 standard deviations from the average (depicted by yellow dots in Figure 2). Next, we regressed these 23 values against vitamin D intake to yield the lower prediction limit (red line in Figure 2). This regression line revealed that 600 IU of vitamin D per day achieves that 97.5% of individuals will have serum 25(OH)D values above 26.8 nmol/L rather than above 50 nmol/L which is currently assumed. It also estimated that 8895 IU of vitamin D per day may be needed to accomplish that 97.5% of individuals achieve serum 25(OH)D values of 50 nmol/L or more. As this dose is far beyond the range of studied doses, caution is warranted when interpreting this estimate. Regardless, the very high estimate illustrates that the dose is well in excess of the current RDA of 600 IU per day and the tolerable upper intake of 4000 IU per day [1].

The public health and clinical implications of the miscalculated RDA for vitamin D are serious. With the current recommendation of 600 IU, bone health objectives and disease and injury prevention targets will not be met. This became apparent in two studies conducted in Canada where, because of the Northern latitude, cutaneous vitamin D synthesis is limited and where diets contribute an estimated 232 IU of vitamin D per day [12]. One study estimated that despite Vitamin D supplementation with 400 IU or more (including dietary intake that is a total intake of 632 IU or more) 10% of participants had values of less than 50 nmol/L [13]. The second study reported serum 25(OH)D levels of less than 50 nmol/L for 15% of participants who reported supplementation with vitamin D [14]. If the RDA had been adequate, these percentages should not have exceeded 2.5%. Herewith these studies show that the current public health target is not being met. We recommend that the RDA for vitamin D be reconsidered to allow for appropriate public health and clinical decision-making.

update 1 March 2015: Screening for Vitamin D Deficiency: Is the Goal Disease Prevention or Full Nutrient Repletion?

Since its founding, the USPSTF has sought to provide a firm evidential base for early detection strategies, evaluating such screening methods as mammography and prostate-specific antigen testing. Although it has also evaluated a few interventions, its predominant focus has been testing for markers that identify persons at risk who are likely to benefit from preventive action. Only recently has the USPSTF ventured into the field—or perhaps the minefield—of nutrition, a territory distant from screening tests and risk assessment, with different and unfamiliar landmarks.

The USPSTF presents its conclusions on testing for vitamin D deficiency (1), reporting that it was unable to find evidence for or against such testing. It noted that one of the likely reasons was the absence of a scientific consensus on both the level of vitamin D status that should be judged “deficient” and what the measurable manifestations of deficiency might be. These are also issues for many other nutrients, such as folate, ascorbate, calcium, and protein. Vitamin D may have seemed to offer a way out of this confusion because serum 25-hydroxyvitamin D [25-(OH)D] concentration is generally recognized as one of the best indices of status for any of a broad array of nutrients. Also, it is now readily measurable and widely utilized.

One of the reasons its promise has not been realized is that most studies of vitamin D efficacy have used a disease-avoidance model, which is the standard approach used by the Institute of Medicine (IOM) for most nutrients (2). Furthermore, disease prevention is the explicit focus of the USPSTF. Nevertheless, the IOM and USPSTF approaches effectively equate health with the absence of disease, an equivalence that nutritionists have long rejected. Instead, nutritionists focus on full nutrient repletion when possible. The inevitable gap between disease prevention and nutrient repletion is still largely unexplored territory. For many nutrients, it can be surprisingly wide, as suggested in this case by studies of the intake required to provide vitamin D in human breast milk in quantities sufficient to meet the needs of infants (3). The IOM’s adult requirement for vitamin D is 600 IU/d (4), which is judged to be sufficient to protect against osteoporotic fracture. In contrast, quantitative and empirical evidence indicates that vitamin D intake from breastfeeding needs to be approximately 6000 IU/d (3, 5). Although high compared with the adult recommendation, such an intake almost exactly reproduces the measured vitamin D status of contemporary Africans leading ancestral lifestyles (6). Such populations provide perhaps our best window on vitamin D levels prevailing during the millennia over which human physiology was adapted to its environment by natural selection.

Whatever the actual requirement or 25-(OH)D cutoff may be, there is another likely reason that the evidence is unclear. The USPSTF drew from systematic reviews and meta-analyses of studies of vitamin D effects, such as the one accompanying the current report (7). In general, the criteria for including studies in such reviews are methodological rather than biological. Of the 6 published biological criteria (8) for including published reports in meta-analyses, the review published in this issue met only 2 (comparable basal status and same chemical form), and several of its component studies met none. Including studies that could never have been informative in the first place (especially when they are large) inevitably biases any review toward the null.

What seems not to have been widely appreciated is that vitamin D exhibits flat response regions at both low and high values of vitamin D status, with a sharp rise in the approximate center of the physiologic range of 25-(OH)D values (8). Studies like the WHI (Women’s Health Initiative), which enrolled women with low vitamin D status values and used a vitamin D dose insufficient to move them into the response range, provide little useful information about vitamin D efficacy. Yet, precisely such studies were included in the review by LeBlanc and colleagues (7). This is not to criticize the WHI, which was designed more than 20 years ago (before vitamin D pharmacology was well-understood), but it is to criticize contemporary reviews and meta-analyses that fail to take advantage of newer information or to use critical biological criteria (8) for selection of studies for analysis of biological effects.

In addition, a disease-avoidance approach becomes problematic for micronutrients in general (and vitamin D in particular) when one understands that micronutrients do not actually cause any of the effects simplistically attributed to them. Although necessary for cell response, such micronutrients by themselves do not initiate or cause the response concerned. For example, vitamin D is a component of the biochemical apparatus that opens the genome to allow access to DNA information needed for a particular cell or tissue response. In terms of cell function, this dependence means that when supplies of the micronutrient are inadequate, cellular response is blunted. This is dysfunction, but not clinically manifest disease. Such dysfunction may indeed lead ultimately to various diseases, but disease prevention remains a dull tool for discerning the defect, and a disease-prevention approach clearly does not measure whether the organism has enough of the nutrient to enable appropriate physiologic responses, such as lactation.

Finally, and aside from the USPSTF’s findings, one must ask whether treating without first testing is sound practice. Certainly, it would be rational to do so if the condition being treated is prevalent and the treatment is safe and inexpensive. That is the case with another micronutrient, iodine, and the iodination of salt. However, the current situation is different because consuming sufficient iodine generally does not require conscious adherence to a particular regimen, whereas taking vitamin D does. Usually, testing improves patient adherence because it provides patient-specific, personally applicable information. General assurances that one probably needs extra vitamin D are not as compelling a motivator as knowing one’s number. Thus, whether the practitioner adheres to the widely divergent guidelines of the IOM (4), the Endocrine Society (9), or the American Geriatrics Society (10), measuring vitamin D status seems to be warranted, not so much to diagnose deficiency but to determine patient status relative to the selected guideline.

update 12 Jan 2015 As the poet Juvenal (died 130AD) wrote: Mens sana in sano corporis– a healthy mind in a healthy body. Its great how the prime antistress homeostatic hormones- a pinch of natural melatonin at night, with ENOUGH daytime anabolic soltriol calciferol vitamin D3, restores good sleep, orchestrate homeostasis of all other hormones especially of the crucial adrenals and gonadals and thus thyroid hormones. ..

Thanks to global human (mostly male) greed enslaving the masses the past 7 millennia ie since at least Sumerian times, we have moved rapidly in our lifetime post WW2 from global homeostatic (food, commodities) plenty to a world of dyshomeostasis- cacostasis stress chaos – in most countries from Afghanistan to Zimbabwe. Just a few years ago South Africa led Africa in productivity and skills, and still has the biggest reserves of riches- minerals- in the world; with boundless natural power (sun, sea) and manpower to drive industry and food production. But in 20 years post apartheid, the ruling ANC under Mbeki and the Zumas has with selfserving treasonous greed brought South Africa to its knees with cacostasis, destruction of continuous water, electricity ; school education, organized and quality food provision ie agriculture, social security, the post office, the national airline, health services, Home Affairs and pensions). Now there are rapidly increasing functionally illiterate or old 16 million on state grants supported by the 6 million capable of meaningfully working and paying taxes if they dont emigrate. And state grants have now been extended to age 23yrs because state school leavers are practically unskilled for anything but being labourers. .

The national powergrid and oil reserves have been degraded so that total indefinite blackouts are now imminent, never mind weekly “outages” crippling work- the economy – and destroying appliances. Never mind increasingly pandemic influenza and HIV, antibiotic resistance puts us in the post-antibiotic era in this age of deadly resistant TB and STDs, with reckless immoral leaders like Zuma and Vavi leading the mob in extramarital sex and provoked violence. .

So as never before, everyone from conception to grave needs realistic regular vitamin D3 supplement at about R3 a month to bolster mental and physical health of children, mothers and the working , never mind the ailing aging, to reduce illhealth costs. . Stress- through raised thyroid, sympathetic and cortisol levels and depressed gastrointestinal, cardiovascular, musculoskeletal and immune control, grossly disrupts homeostasis and shifts victims into catabolic estrogen-dominance , insulin resistance mode- which only the hormone supplements D3 and melatonin, and the essential vitamins and minerals if not risk-laden androgenics can try to balance,

George Chrousos ea. University Athens, Greece since Nat Rev Endocrinol.2009 and now Neuroimmunomodulation. 2015 write: Stress – glucocorticoids – and disorders of the stress system- cacostasis vs homeostasis. All organisms must maintain complex dynamic equilibrium- homeostasis- which is constantly challenged by internal or external adverse forces – stressors. Stress occurs when homeostasis is threatened or perceived; homeostasis is re-established by various physiological and behavioral adaptive responses. Neuroendocrine hormones have major roles in the regulation of both basal homeostasis and responses to threats, and are involved in the pathogenesis of diseases characterized by cacostasis – dyshomeostasis. The stress response is mediated by the stress system, partly located in the central nervous system and partly in peripheral organs. The central, greatly interconnected effectors of this system include the hypothalamic-pituitary-adrenal (HPA) axis and hormones arginine vasopressin, corticotropin-releasing hormone and autonomic norepinephrine centers in the brainstem. Optimal basal activity and responsiveness of the stress system is essential for a sense of well-being, successful performance of tasks, and appropriate social interactions. By contrast, excessive or inadequate basal activity and responsiveness of this system might impair development, growth and body composition, and lead to a host of behavioral and somatic pathological conditions.. Glucocorticoids, the end-products of the HPA axis, play a fundamental role in the maintenance of both resting and stress-related homeostasis and, undoubtedly, influence the physiologic adaptive reaction of the organism against stressors. If the stress response is dysregulated in terms of magnitude and/or duration, homeostasis is turned into cacostasis with adverse effects on many vital physiologic functions, such as growth, development, metabolism, circulation, reproduction, immune response, cognition and behavior. A strong and/or long-lasting stressor may precipitate and/or cause many acute and chronic diseases. Moreover, stressors during pre-natal, post-natal or pubertal life may have a critical impact on our expressed genome.

VITAMIN D ECONOMY & GOAL OF SCREENING: Heaney andArmas, Creighton University QUANTIFYING THE VITAMIN D ECONOMY: Nutrition Reviews Dec 2014; and Screening for Vitamin D Deficiency: Is the Goal Disease Prevention or Full Nutrient Repletion? Ann Intern Med.Nov 2014 write:sunlight and food contribute only modestly to the relevant optimal total serum vit D and 25OHvit D levels: unsupplemented individuals who average blood 25OHvit D of 20 ng/mL are receiving about 2,000 IU/day from nonsupplement sources (i.e food and sun) – whites double the amount compared to dark blacks from skin. . It has been established for 30 years that in fair-skinned individuals, a single exposure to UV-B at one whole-body minimum erythema dose can produce a rise in serum 25D that is equivalent to an oral dose of D3 in the range of 10,000 to 25,000 IU, ie by as little as 10–15 min of whole-body exposure at mid-day in mid-summer in a pale-skinned individual. Pale-skinned northern Europeans show a rise in serum 25D of 9 ng/mL (23 nmol/L) at the end of 4 weeks of exposure. By contrast, in dark-skinned individuals, the rise was half ie 4.5 ng/mL . Meat eaters exhibit higher human 25D status . Input gaps left after estimating solar inputs (on the order of 1,300–1,600 IU/day, as noted above) could well be filled by hitherto unrecognized food sources. For example, Taylor et al.21 report a combined (D3 plus 25D) content of 112 IU vitamin D equivalents for 200 g of beef tenderloin or an egg, associated with 2 ng/mL greater level of serum 25D. The Grassroots Health project collects data on supplement type and has found no difference in the 25D concentration achieved with either 5,000 or 10,000 IU daily doses, irrespective of whether the D3 was delivered via a gel cap in oil or as dry powder in a tablet (unpublished data; S. McDonnell, personal communication). vitamin D could be absorbed from orange juice. On the other hand, fat malabsorption syndromes are known to lead to vitamin D deficiency, and the mechanism is generally considered to be a specific impairment in the absorption of fat-soluble vitamin D. However, poor absorption may reflect not so much mucosal dysfunction, as simple sweeping of any fat-soluble compound out of the gut, dissolved in the unabsorbed fat. Dawson-Hughes et al.,35 using pharmacokinetic methods in individuals with normal absorptive function, reported equal absorbability for D3 under fasting and high-fat meal conditions, with slightly better absorption from a low-fat meal. Mulligan and Licata,36 in an observational study of 17 poor responders to oral D preparations, reported greater absorption from a large meal containing fat than from intake on an empty stomach. However, the limited data, taken as a whole, suggest that the effects of dosage form or vehicle are probably small.

Finally, the issue of D2 versus D3 needs brief mention. Formerly considered controversial, there now seems to be a growing consensus37 that, for equimolar quantities, orally administered D3 raises serum 25D by about twice as much as D2.38–42 This has been shown for bolus doses, short-term continuous administration (12 weeks), and long-term continuous administration (12 months).

Intestinal absorption of D3 is mainly from the jejunum and ileum. Absorbed vitamin D can be found in both the portal venous blood and the lymph that drains the small intestine. The lymphatic pathway may have particular physiological significance for orally acquired vitamin D, since it avoids a first pass of the absorbed vitamin D through the liver. This suggests that the quantitative relationship between vitamin D and 25D will be the same regardless of whether vitamin D enters from the skin or the gut.

Diffusion from the skin into the blood is slow, with a half-time of about 3 days.7 This half-time means that when regular sun exposure is the principal source of D3, serum D3 concentration will be essentially constant.

it is reasonably certain that the concentration of vitamin D in fat tissue is substantially higher than the concentration in serum. – a given volume of fat tissue contains approximately 12 times as much vitamin D as the same volume of serum. However, a several-fold gradient is not surprising as D3 solubility in fat is effectively limitless, while DBP capacity, which is large, is finite.

Assuming a diffusional mechanism and a total body fat mass of 35% of body weight, total body stores in an individual weighing 70 kg would range from 900 to 2,800 µg (37,000 to 113,700 IU). Using the calculations set forth in the prior section and applying them to an individual with a serum 25D level of 20 ng/mL, whose metabolic consumption would be ∼2,000 IU vitamin D/day, the total amount in the reservoir would provide enough of a reserve for 18–57 days at that same rate of utilization. At a serum 25D level of 40 ng/mL, that same reserve would support consumption for only 9–28 days. Neither estimate comes close to compensating for the “vitamin D winter” of most temperate latitudes. The smallness of this reserve explains why even outdoor summer workers who had high daytime skin exposure experienced reductions in 25D averaging approximately 20 ng/mL (50 nmol/L) by late winter. Of note, their 25D values had reached >50 ng/mL (125 nmol/L) by late summer, which is roughly the same as that reported for East Africans living ancestral lifestyles.48 This study indicates both that existing stores at the end of summer were not adequate to maintain the achieved summer level and that the late winter level (∼30 ng/mL) represented a utilization of approximately 3,000 IU/day.

Chemical partition Extracellular 25(OH)D The first step in the chemical conversion of D3 is 25-hydroxylation.Bikle et al.51 showed that skin cells contain all the requisite enzymatic apparatus to produce both 25D and 1,25D. However, it is doubtful that under ordinary circumstances, skin is a major source of the extracellular 25D measured in serum (D. Bikle, personal communication). Other sources remain to be identified.

The efficiency with which D3 is converted to 25D varies widely from individual to individual. Various reasons can be put forth for these inter-individual differences that, though studied in somewhat less detail, have been reported by many investigators. One example is the variable methylation of the CYP2R1 gene and, hence, variable expression of the hepatic 25-hydroxylase.53 While there is currently no final answer, it is clear that differences in intestinal absorption of D3 could not explain the slow rise in participant B, relative to participant A. Moreover, the internal consistency in the shape of the respective curves virtually excludes methodological variability as a cause of the difference.

Extracellular 1,25(OH)2D The second hydroxylation, which produces extracellular 1,25D, occurs predominantly in the proximal convoluted tubular cells of the kidney. While 25-hydroxylation is not highly regulated, the opposite is true for 1,25D, the synthesis of which is upregulated by parathyroid hormone and low serum inorganic phosphorus concentration and downregulated by fibroblast growth factor-23. Note that 1,25D is a principal regulator of intestinal absorption of calcium; during this process, it acts by upregulating expression of the calcium transport apparatus of the enterocyte. This is an endocrine effect as it is mediated through serum endocrine-like activity and exhibits a typical negative feedback control loop. Under usual conditions, 1,25D is necessary for regulation of calcium absorption. However, it is not the only factor involved in this process. It should also be noted that in the absence of other vitamin D metabolites, 1,25D by itself has been reported not to be sufficient to elevate intestinal calcium absorption.55,56

As would be expected for regulator molecules, the serum half-time of 1,25D is short (hours). Its concentration in serum is a reflection mainly of relative calcium need—being high in individuals on low-calcium diets or in those with calcium malabsorption and low in individuals with high calcium intakes. Also, 1,25D has long been recognized to be calcemic when used therapeutically. The mechanism is generally attributed to intestinal calcium absorption, but this cannot be a satisfactory explanation, as increased metabolic input alone (i.e., without considering output) is rarely sufficient to elevate the serum concentration of any metabolite. Moreover, 1,25D and its analogs do not elevate calcium absorption in patients with end-stage renal disease,57 a condition in which the calcemic effect of 1,25D is often readily apparent. While not adequately explored, there remains another possibility, i.e., an effect of 1,25D on bone-lining cells, where a fall in bone fluid pH to just below 7.0 is enough to solubilize bone mineral sufficiently to elevate serum calcium.58 Physical partition

The distinction between the endocrine and the autocrine pathways is one aspect of the physical partition between extracellular and intracellular processing of the vitamin. The prevailing assumption seems to be that most or all of the D3 entering the body is 25-hydroxylated and that the resulting 25D circulates in the blood, where it serves as the substrate for both renal and extrarenal 1 -α-hydroxylation, with the renal 1,25D product circulating in the blood like 25D and with the extrarenal 1,25D never being expressed in the only accessible body compartment, i.e., the blood.

As Hollis and Wagner59 have pointed out, D3 enters cells more readily than does 25D and, as noted above, there are several enzymes other than the hepatic CYP2R1 that are capable of 25-hydroxylation of D3.49,50 Hence, a physical partition of the vitamin D pathways prior to the 25-hydroxylation step has to be given serious consideration. That this is more than just a theoretical possibility is suggested by the fact, noted earlier, that oral 25D elevates serum 25D to a substantially greater extent than does oral D3.28–30 This was shown first by Barger-Lux et al.28 in a 10-week dosing study involving the two molecules. Figure 9 plots the 25D response to the two agents observed in a group of 54 healthy adults and shows a clear divergence of the dose response curves, with a greater than seven-fold difference in slopes. Cashman et al.,30 using a different design, found an approximate five-fold difference in response after 10 weeks of dosing, and Bischoff-Ferrari et al.,29 an approximate four-fold difference after 17 weeks of dosing.

Figure 9 Change in serum 25D plotted as a function of intake for varying oral doses of 25D and D3. Data from Barger-Lux et al.28 That there should be a greater rise in 25D when oral 25D is the source is, in a sense, trivial, as oral 25D is immediately reflected in the serum, while oral vitamin D must first be 25-hydroxylated, a process that, as described above, is necessarily slower, sometimes substantially so. Only a proper pharmacokinetic study that compares area-under-the-curve values for the two agents can fully quantify this difference. Such a study must either be long enough to allow the 25D plateau to be reached while on continuous dosing of D343 or, if using a bolus dose design, must follow the time course for the two agents for probably 4 months so as to allow full 25-hydroxylation of the administered D3 and full consumption of the administered 25D. No such data are currently available, and this aspect of the physical partition must remain speculative. Nevertheless, the issue is an important one, not just for the therapeutics of 25D but also for a full understanding of the vitamin D economy (see below).

The 25D half-time (as measured by Clements et al.60–62 using tracer-labeled 25D) presents certain puzzling features in its own right. A half-time of, say, 20 days (toward the lower end of the range found by Clements et al.) translates to a daily turnover of about 3.47% of the total mass of extracellular 25D. If the size of daily utilization is known, it is possible to calculate the size of the 25D mass from that fractional utilization rate. If all of the vitamin D input to the body is converted to extracellular 25D, then at a serum 25D concentration of 20 ng/mL (requiring, as shown above, a daily input of ∼50 µg), that 50-µg input is numerically equal to the daily turnover. So, total 25D mass would be 50/0.0347, or close to 1,500 µg. This figure is larger by an order of magnitude than that of the measurable total serum content of 25D, and the discrepancy becomes even larger at higher serum 25D concentrations or longer half-times. This seeming discrepancy has not been noted previously, with one potential reason being the computational difficulty of harmonizing biological units (IU), first with mass concentrations (µg/mL), then with SI units (nmol). However, if a substantial fraction of daily input of D3 is 25-hydroxylated intracellularly, after which it is immediately activated to 1,25D, then only the 25D in the extracellular compartment would be labeled by a tracer-based approach to kinetic analysis, and the calculated daily utilization of the circulating 25D would be lower and the corresponding 25D mass estimate would be closer to what is known from blood and soft tissue content. These calculations provide support for the suggestion of Hollis and Wagner59 that “parent compound D” has more functional significance than has usually been thought.

There is one quantitative aspect of the physical partition, whether occurring prior to or after the 25-hydroxylation step, which seems inescapable. Whether one takes as optimal a serum 25D concentration of 20 ng/mL or 40 ng/mL, the molar equivalent D3 inputs required to sustain either level are far higher than the moles of 1,25D required to support the calcium economy. As noted above, a serum 25D of 40 ng/mL requires approximately 4,000 IU/day, or 100 µg/day, and a serum 25D of 20 ng/mL requires approximately 2,000 IU/day, or 50 µg/day. By contrast, the calcium economy requires between 0.5 µg and 2.0 µg of 1,25D/day. (Higher doses, as noted above, produce hypercalcemia.) It follows that >90% of D3 utilization is occurring along the intracellular/autocrine pathway. If that is not the case, then most of the D3 input to the body is degraded metabolically and not used at all. The latter possibility seems quite improbable, particularly in view of the marginal or subadequate vitamin D status that seems nearly universal. Answering this question of the relative potency of oral D3 and 25D will illuminate the partition of D3 between the extracellular and intracellular pathways and will be an important step in unraveling the puzzle of the physical partition.

One instance in which the pre-25D intracellular pathway is operative is the transfer of vitamin D activity into human breast milk.59,63 25D does not transfer across the secretory mucosa of the mammary gland with sufficient efficiency to produce enough vitamin D activity in milk to nourish the infant, while D3 does. However, for this to occur, D3 must be present in the blood that bathes the mammary secretory apparatus. In earlier work, Hollis et al.63 showed that the concentration of vitamin D in human milk was about 28% of the concentration of D3 in maternal blood. In subsequent work (B. Hollis, personal communication), that figure was shown to be closer to 32%, and a recent study by Oberhelman et al.64 showed a transfer fraction that can be calculated to be about 44%. Based on recommendations of both the American Academy of Pediatrics and the Institute of Medicine for infant intake (400 IU vitamin D/day, which requires a milk concentration of about 520 IU/L, i.e., ∼34 nmol/L), these transfer fractions would require a maternal serum vitamin D concentration of about 30–40 ng/mL (78–120 nmol/L). (The corresponding 25D concentration would be >50 ng/mL [125 nmol/L]; see Figure 8.) Hollis and Wagner59 estimate that the total input of D3 needed to maintain a milk concentration sufficient to meet the infant’s needs for vitamin D was approximately 6,000 IU/day. The equivalence value derived above produces a needed input of approximately 6,000 IU/day, which is essentially identical to the empirical estimate of Hollis and Wagner. Dosing schedules and serum D3 concentrations

Dosing frequency for oral vitamin D supplementation regimens will affect serum concentration of D3 in predictable and often very striking ways. This fact has been largely overlooked to date, as the serum concentration of D3 has been generally considered to be of no particular interest in its own right. The rationale for infrequent (or bolus) dosing is that it leads to better adherence and that an excess amount ingested today will be stored in fat for use tomorrow. However, this assumption overlooks the effect of infrequent dosing regimens on D3 blood concentrations.

Serum D3 has a half-time variously estimated to be in the range of 0.5–3.5 days, with most investigators favoring a value of about 1.0 days. In contrast, D3 produced in skin moves into the blood with a half-time of about 3 days. This means that when skin synthesis is the principal source of D3, serum D3 concentration will be essentially constant around the clock, as D3 input to the blood from the skin (though produced mainly at mid-day) is effectively constant. With oral ingestion, intestinal absorptive input of D3 occurs mainly during a 4-h period following ingestion. (In one study, a TMAX of as much as 12 h was reported.65 As this is well beyond the usual mouth-to-cecum transit time, the 12-h figure, if confirmed, would suggest appreciable colonic absorption, or small bowel mucosal retention, or a delay pool in the intestinal lymphatics.) In any case, assuming a 1.0-day half-time, serum D3 concentration will inevitably follow a sawtooth pattern, particularly if oral ingestion is the principal input. Figure 10 displays the patterns for purely cutaneous input and for daily, weekly, and biweekly oral administration. With a once-a-week schedule, as is evident from Figure 10, serum D3 concentrations are close to zero for several days each week and below the reference level for most of the interdose interval. Thus, in the practical order, a nursing woman who takes her total weekly dose of vitamin D once each week would produce milk with little or no D content for roughly 4 of the 7 days in each week. This irregular delivery will be even more pronounced with biweekly or less frequent dosing schedules.

Figure 10 Calculated time courses for serum D3 concentration for varying oral dosing intervals. The reference level is the serum concentration for continuous (as contrasted with intermittent) dosing. Each dosing scheme provides the same cumulative intake, according to one of the following regimens: once daily, or 7 times the daily intake once weekly, or 14 times the daily intake once every 2 weeks. It should be stressed that Figure 10 illustrates the concept and is not a depiction of actually measured serum concentrations of D3. Under input conditions in excess of daily use, unused D3 will accumulate in fat, and its concentration there would be predicted to damp the oscillations of D3 concentration in serum to some extent.

An additional feature of interval dosing is the high D3 concentration peaks achieved in the days following each dose. The impact of such high D3 levels is unclear, although Vieth66 has pointed to the induction of the 24-hydroxylation pathway as a likely consequence, with a corresponding reduction in effective vitamin D activity. Further, as the binding capacity of DBP is approximately 4.7 µmol67 (or ∼78,000 IU/L), with true Stosstherapie, as in several recent studies,68,69 the DBP will be fully saturated by the ingested D3, resulting in displacement of both 1,25D and 25D off DBP and into circulation as free or unbound moieties for several days after dosing (i.e., until fat uptake lowers serum D3 sufficiently). This effect amounts to a transient vitamin D intoxication of uncertain physiological import. Unfortunately, there is essentially no published information about vitamin D concentrations in the immediate post-dosing period following large bolus doses. Whatever else may be said of Stosstherapie, it certainly is not physiological. Factors influencing serum 25D concentration

Aside from the possible importance of D3 concentration as the substrate for autocrine activity of vitamin D, there is general agreement that serum 25D concentration is currently the principal indicator of vitamin D status.70 This is because extrarenal conversion of 25D to 1,25D operates at concentrations below the kM for the tissue 1 -α-hydroxylases; hence, serum 25D concentration limits the amount of 1,25D a tissue can synthesize when its cells are stimulated to produce a vitamin D-dependent response. While there is no consensus as to the optimal serum 25D concentration, there is also no disagreement about the importance of the substrate, regardless of which concentration may be deemed optimal.

Input of D3, a factor that manifestly affects 25D concentration, has been the subject of much of the previous discussion. Attention is now focused on the effect on serum concentration of 25D produced by variations in body size and in D3 output, i.e., utilization and/or degradation of the 25D in serum. Obesity

One widely recognized influence on 25D concentration is obesity, with serum 25D being lower in obese individuals. This was originally attributed to a phenomenon termed “sequestration” (implying trapping of vitamin D in adipose tissue of obese individuals).71 However, Drincic et al.72 have shown that simple volumetric dilution is both a more logical explanation and one that fully explains the weight-based difference. Curiously, body mass index works in various regression models almost as well as body weight (and somewhat better in some datasets). This is surprising as body mass index is not a measure of mass but of fatness. The reason is presently unclear, and this observation suggests the possible existence of further mechanisms operating in obese individuals. Parathyroid hormone-1,25D axis Clements et al.60–62 showed that 25D half-time in serum ranged from 15 to >35 days, with 25D half-time being inversely related to parathyroid hormone concentration. The parathyroid hormone effect, noted both in patients with hyperparathyroidism and in animals subjected to calcium deprivation, was, in turn, mediated by serum 1,25D concentration. Why 25D utilization (or degradation) should rise in the face of calcium need is physiologically unclear, particularly as renal 1,25D synthesis is not as dependent on 25D concentration as the autocrine functions of vitamin D.

Inflammation. The other major influence on serum 25D concentration is inflammation. It has been reported that vitamin D status is reduced in the face of systemic inflammatory processes.73–78 For example, Duncan et al.75 reported an inverse correlation of 25D with serum C-reactive protein, with 25D being 40% lower as serum C-reactive protein rose from <5 mg/L to >80 mg/L. Autier et al.,79 in a metaanalysis of the several reports on this relationship, confirmed the existence of the association but attributed the reduced vitamin D status to underlying illness rather than to the inflammation itself. That conclusion may be partly correct, at least for some chronic illnesses, but it cannot apply to the many documented cases in which vitamin D status drops acutely across an inflammatory episode, as with total knee arthroplasty.73,77 In one case study, Henriksen et al.73 reported a 12% drop in 25D by day 2 after total knee arthroplasty and a nearly 80% drop by post-surgery week 8. Reid et al.77 evaluated a series of 33 patients who underwent total knee arthroplasty and reported an approximate 40% drop in total 25D and a 33% drop in calculated free 25D by day 2 after surgery, which was associated with large increases in C-reactive protein.

Decreases in 25D of this magnitude and rapidity cannot be explained by decreased synthesis and must, therefore, reflect increased utilization, degradation, or loss. Depending on which values may be estimated for the total 25D mass (see above), reductions in 25D concentration of the size reported by Reid et al. translate to a loss of several hundred micrograms from the body, which is substantially greater than ordinary daily utilization of vitamin D. While increased utilization cannot be ruled out, it seems unlikely to be the sole explanation. Another possibility, which was suggested by Waldron et al.,76 is the loss of DBP (with its bound ligand) in the urine. In 30 patients undergoing elective orthopedic surgery, the ratio of DBP to creatinine in urine rose 2.5× by the second day post-surgery; this was associated with a >20-fold increase in C-reactive protein. Renal loss could certainly explain much or all of the change in 25D observed in these studies and could be the result of interference with the kidney’s megalin–cubilin system, possibly produced by the anesthesia or inflammatory cytokines associated with the surgery.

Although not directly related to the major focus of this review, the conclusion reached by several of the authors of the studies just reviewed, i.e., that, while inflammation clearly reduced D status, this reduction was without nutritional significance, is in no way supported by data in any of the papers concerned, nor is it consistent with the importance of serum 25D concentration as the principal limiting factor in the autocrine pathway.

METABOLISM AND UTILIZATION the data assembled here make clear that, even with today’s widespread vitamin D inadequacy, total vitamin D inputs are far higher than previously thought, food sources are greater than previously recognized, and solar input, though theoretically capable of fully meeting any plausible vitamin D requirement, is actually only a minor present-day contributor to total vitamin D input at the population level. That does not mean that the human requirement is more easily met. Rather, it indicates that the requirement is higher than previously recognized, with populations still short of meeting that requirement by the amount needed to move prevailing serum 25D concentrations from current values to putatively healthier levels.

These analyses also make clear that at prevailing inputs (i.e., <4,000 IU/day), D3 is rapidly 25-hydroxylated and little D3 circulates in the blood or is shunted into adipose tissue for storage. Additionally, the recent recognition that oral 25D may raise serum 25D to a significantly greater extent than does oral vitamin D suggests the possibility of a hitherto little recognized or explored intracellular pathway in which the entire metabolic sequence is handled within certain target tissues and is not reflected in blood. A related finding in this respect is the importance of a maternal serum D3 concentration sufficient to support production of human milk capable of meeting infant needs for vitamin D.

Several of these insights have implications for the human requirement. For example, the vitamin D input needed to support an adequate amount of vitamin D in human milk has implications not just for lactation but also for human success as a species under presupplementation conditions. Inadequate vitamin D input in newborns would be expected to lead to skeletal abnormalities (for which the paleo-fossil record provides no evidence), in addition to possible consequences for immune system development.89 A total input of approximately 6,000 IU in modern humans equips them to feed their infants with a nearly full range of the nutrients needed for healthy growth.

CONCLUSION Precise quantification of vitamin D inputs, transfers, conversions, and compartment sizes are essential for a full understanding of how the human body utilizes this essential micronutrient, why it is important, and what the consequences are of an inadequate vitamin D input.

Since its founding, the U.S. Preventive Services Task Force (USPSTF) has provided firm evidential base for early detection strategies, evaluating such screening methods as mammography and prostate-specific antigen testing. Although it has also evaluated a few interventions, its predominant focus has been testing for markers that identify persons at risk who are likely to benefit from preventive action. Only recently has USPSTF entered the (mine)field of nutrition, a territory distant from screening tests and risk assessment, with different and unfamiliar landmarks.

The USPSTF now reports it is unable to find evidence for or against vitamin D deficiency testing (1), the likely reasons being the absence of a scientific consensus on both the level of vitamin D status that should be judged “deficient” and what the measurable manifestations of deficiency might be. These are also issues for many other nutrients, such as folate, ascorbate, calcium, and protein. Vitamin D may have seemed to offer a way out of this confusion because serum 25-hydroxyvitamin D [25-(OH)D] concentration is generally recognized as one of the best indices of status for any of a broad array of nutrients. Also, it is now readily measurable and widely utilized.

One of the reasons its promise has not been realized is that most studies of vitamin D efficacy have used a disease-avoidance model, which is the standard approach used by the Institute of Medicine (IOM) for most nutrients (2). Furthermore, disease prevention is the explicit focus of the USPSTF. Nevertheless, the IOM and USPSTF approaches effectively equate health with the absence of disease, an equivalence that nutritionists have long rejected. Instead, nutritionists focus on full nutrient repletion when possible. The inevitable gap between disease prevention and nutrient repletion is still largely unexplored territory. For many nutrients, it can be surprisingly wide, as suggested in this case by studies of the intake required to provide vitamin D in human breast milk in quantities sufficient to meet the needs of infants (3). The IOM’s adult requirement for vitamin D is 600 IU/d (4), which is judged to be sufficient to protect against osteoporotic fracture. In contrast, quantitative and empirical evidence indicates that vitamin D intake from breastfeeding needs to be approximately 6000 IU/d (3, 5). Although high compared with the adult recommendation, such an intake almost exactly reproduces the measured vitamin D status of contemporary Africans leading ancestral lifestyles (6). Such populations provide perhaps our best window on vitamin D levels prevailing during the millennia over which human physiology was adapted to its environment by natural selection.

Whatever the actual requirement or 25-(OH)D cutoff may be, there is another likely reason that the evidence is unclear. The USPSTF drew from systematic reviews and meta-analyses of studies of vitamin D effects, such as the one accompanying the current report (7). In general, the criteria for including studies in such reviews are methodological rather than biological. Of the 6 published biological criteria (8) for including published reports in meta-analyses, the review published in this issue met only 2 (comparable basal status and same chemical form), and several of its component studies met none. Including studies that could never have been informative in the first place (especially when they are large) inevitably biases any review toward the null.

What seems not to have been widely appreciated is that vitamin D exhibits flat response regions at both low and high values of vitamin D status, with a sharp rise in the approximate center of the physiologic range of 25-(OH)D values (8). Studies like the WHI (Women’s Health Initiative), which enrolled women with low vitamin D status values and used a vitamin D dose insufficient to move them into the response range, provide little useful information about vitamin D efficacy. Yet, precisely such studies were included in the review by LeBlanc and colleagues (7). This is not to criticize the WHI, which was designed more than 20 years ago (before vitamin D pharmacology was well-understood), but it is to criticize contemporary reviews and meta-analyses that fail to take advantage of newer information or to use critical biological criteria (8) for selection of studies for analysis of biological effects.

In addition, a disease-avoidance approach becomes problematic for micronutrients in general (and vitamin D in particular) when one understands that micronutrients do not actually cause any of the effects simplistically attributed to them. Although necessary for cell response, such micronutrients by themselves do not initiate or cause the response concerned. For example, vitamin D is a component of the biochemical apparatus that opens the genome to allow access to DNA information needed for a particular cell or tissue response. In terms of cell function, this dependence means that when supplies of the micronutrient are inadequate, cellular response is blunted. This is dysfunction, but not clinically manifest disease. Such dysfunction may indeed lead ultimately to various diseases, but disease prevention remains a dull tool for discerning the defect, and a disease-prevention approach clearly does not measure whether the organism has enough of the nutrient to enable appropriate physiologic responses, such as lactation.

Finally, and aside from the USPSTF’s findings, one must ask whether treating without first testing is sound practice. Certainly, it would be rational to do so if the condition being treated is prevalent and the treatment is safe and inexpensive. That is the case with another micronutrient, iodine, and the iodination of salt. However, the current situation is different because getting sufficient iodine generally does not require conscious adherence to a particular regimen, whereas taking vitamin D does. Usually, testing improves patient adherence because it provides patient-specific, personally applicable information. General assurances that one probably needs extra vitamin D are not as compelling a motivator as knowing one’s number. Thus, whether the practitioner adheres to the widely divergent guidelines of the IOM (4), the Endocrine Society (9), or the American Geriatrics Society (10), measuring vitamin D status seems to be warranted, not so much to diagnose deficiency but to determine patient status relative to the selected guideline.

THE NEAR-IMPOSSIBILITY OF OVERDOSING WITH VITAMIN D3 – except by persistent repeated injection: A Report in Feb 2014 from Bansai & Arora ea New Delhi show how extreme the overdose of vitamin D3 must be to cause hypercalcemic toxicity: an Asian woman given 6million iu imi over 10 days after knee surgery presented 2 months later with 6 wks of persistent vomiting, fatigue, with moderate hypercalcemic renal failure and 25OHvit D level of 150ng/ml; that normalized in 2 weeks.. So her peak level after the initial 2 weeks on an average ~50 000iu/day may have been around 500-600ng/ml.. Bansai and Aroraquote two series from endemically vit D deficient Kashmir (Pandita ea 2012 in Jammu and 2011Koul ea Srinagar) of a total 25 elderly given chronic overdoses D3 600 000iu monthly , who were found to have similar moderate hypercalcemia and renal failure with peak 25OHvit D of 100 – 300ng/ml: a mean vit D3 dose of between 20 000iu and >1million iu/day?, mean s. creat 2.5; mean 25OHvitD of 100 – 200ng/ml; mean calcium 13.1mg/dl. 20 000iu a day indefinitely in these frail small elderly averages at least 400iu/kg/day, at least 5 times the chronic recommended dose in the literature the past decades- and to boot, routinely given them with a highdose calcium supplement- when it is rather magnesium that should if any be boosted. . Koul ea do note that about 100 000iu vit D a day ongoing is required to cause hypercalcemia, the mean lethal dose being about 8million iu.

By contrast, previous reports below- eg from the Netherlands report of 2million iu single overdose in 90 year olds; and planned 600 000iu orally monthly dose in Pakistani men wasted with TB (Salhuddin ea below) showed no overdose signs. So a single loading dose of 1 to 2 million units is unlikely to give overload. By these precedents (eg 600 000iu p.o monthly- apparently official policy of the Pakistani Endocrine Society) one may in acute infections give up to 600 000iu as a loading dose (a million in an obese ill patient) in acute infection situations, then 50 000- 80 000iu weekly depending on weight, to maintain level around 90ng/ml.

Am J Clin Nutr March 2008 Pharmacokinetics of a single, large dose of cholecalciferol 100 000iu Ilahi, Armas, and HeaneyCreighton University Medical Center, Omaha, Design: followed for 4 mo, 30 subjects were supplemented with a single oral dose of 100 000 IU cholecalciferol. 10 subjects served as a control group to assess seasonal change of calcidiol. The subjects were healthy with limited sun exposure (<10 h/wk) and milk consumption (<0.47 L daily); excluded granulomatous conditions, liver disease, kidney disease, or diabetes or taking anticonvulsants, barbiturates, or steroids. Results: Serum calcidiol rose promptly after cholecalciferol dosing from a mean (±SD) baseline of 27.1 ± 7.7 ng/mL to a concentration maximum of 42.0 ± 9.1 ng/mL. Seven percent of the supplemented cohort failed to achieve 32.1 ng/mL at any time point. The highest achieved concentration in any subject was 64.2 ng/mL. The control group had a nonsignificant change from baseline of −0.72 ± 0.80 ng/mL during 4 mo. Conclusions: Cholecalciferol (100 000 IU) is a safe, effective, and simple way to increase calcidiol concentrations. The dosing interval should be ≤2 mo to ensure continuous serum calcidiol concentrations above baseline.

THE IMPORTANCE OF IMMUNOSYNERGY BETWEEN ADEQUATE ANABOLIC HORMONES- VIT D3, MELATONIN(Berman 1926, Carrillo-Vico2013), AND PROGESTERONE in planned and current pregnancy, and aging? Thangamani, Kim ea Purdue & Indiana Universitiesin J Immunol. 2014 Dec 29: Cutting Edge: Progesterone Directly Upregulates Vitamin D Receptor Gene Expression for Efficient Regulation of T Cells by Calcitriol. The two nuclear hormone receptor ligands progesterone and vit.D play important roles in regulating T cells.., we report that progesterone is a novel inducer of vit.D receptor (VDR) in T cells and makes T cells highly sensitive to calcitriol even when vit. D levels are suboptimal. This novel regulatory pathway allows enhanced induction of regulatory T cells but suppression of Th1 and Th17 cells by the two nuclear hormones. The results have significant ramifications in effective regulation of T cells to prevent adverse immune responses during pregnancy.

A recent review of vitamin D from Mike Holick (Boston Mass.) and a German team again reminds us of two opposing forces limiting natural sunshine vitamin D supply: on the one hand the skin shuts down active vit D production if the sunlight burns, while on the other, there is simply not enough sunlight beyond 35degrees latitude from the equator. Thus Germany and Canada-northern USA for example, at >45degrees north, get far too little sunlight for vit D needs ; eg London is at 51degrees north; Cape Town-Florida-San Diego, Sydney-Buenos Aires, Hawai and the Med. countries are at the 35degree south latitude. Even this close to the equator, many overdress- especially more observant religious women- and thus minimize benefit from summer sunshine.

Sunshine Cures: why did TB sanatoria work (before there were antibiotics)? was it indeed the boost of copious sunshine secosteroid antimicrobial soltriol in the skin destroying the M TB porphyrins? or was it belief, then-cleaner air, high altitude, rest, care and better nutrition?

A recent 2009 Mt Sinai NY report of a case of CTB cutaneous TB stresses how rare this skin complication is despite the increasing spread of TB with AIDS- perhaps partly because of the higher prevalence of HIV in poorer peoples in sunnier warmer ie relatively better sunshine-cholecalciferol-endowed climates.

We easily make our optimal vit D3 ~100iu/ kg per day living playing and working outdoors in warm lands. But since we dress more in cooler climates, with aging and dress-conservative cover-up tribal eg Arabic and Hasidic and Mormon customs; and avoid sunburn, and from early middle age lose 3/4 of our skin vitamin D production by 70years, we aging thus need the bulk of our vit D requirements as supplements ie ~7000iu/day or 50 000iu/week.

A century ago, TB, polio, measles, scarlatina, and syphilis were rampant, and infections rather than wars killed most – ending in the 1919 flu holocaust that devastated the family of Dr Sir Arthur Conan Doyle (whereas the Flu pandemic took just one of my parents’ score of siblings- and polio just left my Mom with a limp..)..

2014 is the centenary of recent recognition of the cod liver oil antirickets steroid factor – calciferol/soltriol -briefly misnamed “vitamin” D – by McCollum, Davis (USA 1913) and Mellanby(UK); so that in 30 years by 1945, rickets had been all but abolished in USA. But the recognition of the antirachitic factor was facilitated by discovery in the preceding decade of vitamins A, B and C. The antiscurvy benefit of fresh uncooked coloured crops (and thus their juice) had indeed been recognized for millennia – eg the Royal Navy limejuice- , but a specific micronutrient vitamin deficiency was first only recognized in 1907. Vitamin C ascorbic acid identification also took another 25years . For 90 years, it has been recognized that a lightly cooked exclusively fatty meat diet can provide enough vitamin C (let alone all micronutrients) for health in eg atheroma- and scurvy-free Eskimos and anyone who cares to eat thus (Stefansson ) .

Sadly, the lifegiving vitamins have been diluted, all but eliminated from retail bottled codliver oil, a ml of which now generally supplies perhaps only 125iu vit D, and vitamin A 1000iu … So even a tablespoon supplies only about 1200iu vit D.. The Weston Price Foundation discusses why modern commercial codliver oil is good with its balance of vits A and D– but the vitamin D level is still far too low for cooler darker countries. However we recommend, (apart from far cheaper vit D3 powder 50 000iu/1ml scoop) – a tsp cod liver oil at least 3 times a week because it is the cheapest natural- and with Scandinavian manufacturing controls, safe- source of vital EPA+DHA available as well as some vitamins A and E.

As real summer begins here between the southern oceans, cold winter in the northern hemisphere, we must constantly remind that vitamin D3 cholecalciferol is NOT an exogenous vitamin ie a biological nutrient essential (Funk’s ‘vitamine’, shortened by Jack Drummond because they are not amines to the more appropriate ‘vitamin’) in the human diet ( like vits A, B, C, E & K) because humans cannot make them. . But since we make vit D with light exposure of our skin, since most humans dont get enough sunlight on our skin, it is certainly a conditioned essential anabolic steroid, which like other anabolic steroids (the balance especially of androgens) is vital at optimal blood levels through life for optimal health, healthspan.

Unlike the real vitamins and essential minerals, Calciferol is (like eg CoQ10, alphalipoic acid, nitric oxide, EPA and DHA) made in limited quantities in humans with adequate organ function and sunshine; but none of them generally in anywhere near optimal quantities for healthspan against all diseases. So given humans’ capacity to live well to a century, we need such supplements from youth to ensure chronic health so as to die of old age in good health. .

How does this relate to the death this month of Dr Nerissa Pather? Multiresistant TB contracted on duty 12 years ago eventually killed her, whether or not such high-risk people are ever advised to take the best prevention- zinc, selenium, multivites but especially highdose vit C and D3.

D3 bio-insufficiency fragility and dysimmunity is further complicated since to correct it requires both plenty of skin sunshine exposure, eaten vitamin C and it’s daughter cholesterol, and optimal kidney and liver function. Even then optimal vitamin D3 bloodlevel and effect may be blocked by foolhardy cholesterol blockade eg statins, and by excess intake and thus bloodlevel of vitamin D2 ergocalciferol – which authorities eg in South Africa and USA still negligently promote/ dispense as the dangerously misnamed “strong calciferol”. It is indeed D3 cholecalciferol, not D2 that is the miracle sunshine strong calciferol steroid; egocalciferol dominance, like insulin and estrogen dominance, is harmful, and can and must be avoided. .

So it is increasingly apparent that, just as intake/manufacture of vitamin C the true sunshine vitamin (those colourful veg/ fruit orchards etc) , and thence cholesterol, should each be at least a few gms a day, the human (clothed indoor-dwelling) adult synthesis + intake of sunshine hormone vitamin D3 soltriol should be nearer to 10 000iu ie 250mg/day, or more practically 50 000iu vit D3 a week (at a trivial supplement cost of eg R6/month or $5 a year) for a bigger adult- especially in longer darker winter (starting with perhaps about 25000iu every fortnight for babies) .. of course balanced in most societies with the other supplements especially water, vitamin K2, zinc, selenium iodine and magnesium (and iron for children and reproductive mothers) .

So, how many more millions must suffer and die from lack of the cheapest, best, safest conditioned essential antimicrobial antioxidant anabolic nutrients available?

An undated (post 2003) Pharmacology Bulletin from Canterbury NZ at least gives conservative realistic vit D3 advice: a loading dose of D3 500 000iu , then 50 000iu/month. This compares with our routine loading dose of about 200 000 to 400 000iu to start, then 50 000iu every week or two (proportionate to body mass and illness). But Lennons here negligently still continues to advertise their Strong Calciferol datasheet (updated 2004) as calciferol- last year they in fact confirmed it is D2 ergocalciferol, not cholecalciferol. Only their websitehttp://www.ndrugs.com/?s=lennon-strong%20calciferol confirms that their strong Calciferol is D2; whereas they also make low strength D3 tabs.

From today’s press “The South African Medical Association (SAMA) extends heartfelt condolences on the passing of 38yr old Dr Nerissa Pather on 18th December 2014 . Whilst on community service at a Kwazulu Natal clinic, Dr Pather contracted well-publicised multi-drug resistant spinal TB in 2002 , that rendered her paralyzed and in constant pain. The loss to a communicable disease acquired in the course of duty is an incalculable tragedy. SAMA reiterates its call to all health departments and facilities to ensure that basic TB prevention methods are available to all healthcare workers in our facilities. Sadly, this is not the case in many of our hospitals and clinics and continues to place health professionals at enormous risk. The potential consequences of infection and even acquiring drug resistant TB are tragically evident in the death of Dr Pather. SAMA bows its head to a colleague who has paid the ultimate price in caring for her fellow human beings.”

The tragedy is that with general authoritarian nihilism about universal vitamin supplements- some calling their promotion quackery- unrecognized deficiency eg vit D3, rickets, and vit C scurvy are on the increase even in the more affluent eg USA and in sunnier climates- especially with increasing geriatrics and the frail surviving with eg HIV, TB, cancer, chronic bowel disease, gross overuse of warfarin (vit K deficiency) and statin (CoQ10 deficiency) etc. .

Vitamin D Deficiency in Critically Ill Patientsis rarely considered or treated .. N Engl J Med 2009 Lee, Eisman & Center studied vitamin D status in ICU patients referred to St. Vincent’s Hospital, Sydney in 2007. Among approximately 1100 ICU patients per year, the mean 25-hydroxyvitamin D in 42 referred patients was ~17ng per milliliter, with a high prevalence of hypovitaminosis D . Moreover, three patients died (from metastatic thymic carcinoma, glioma, and lymphoma), and had undetectable levels of 25-hydroxyvitamin D. The current study of ICU patients reveals high prevalence of hypovitaminosis D that was associated with adverse outcomes, independently of hypocalcemia and hypoalbuminemia. Supplementation with vitamin D (at a mean dose of 820 IU per day) before admission was not protective. Vitamin D deficiency is associated with increased mortality.However, vitamin D has pleiotropic effects in immunity, endothelial and mucosal functions, and glucose and calcium metabolism. The association between hypovitaminosis D and common conditions (e.g., the systemic inflammatory response syndrome, septicemia, and cardiac and metabolic dysfunctions) in critically ill patients may be important. Vitamin D–deficient and vitamin D–insufficient states may worsen existing immune and metabolic dysfunctions in critically ill patients, leading to worse outcomes. A total of 17% of ICU patients in our study had undetectable levels of vitamin D. hypocalcemia was identified as a reason for referral in only 5% of the patients. These findings highlight the need for consideration of vitamin D status and supplementation in patients in the ICU.

Arch Intern Med. 2008;168:1629-37 25-hydroxyvitamin D levels and risk of mortality in the general population. Melamed , Astor ea. Albert Einstein College of Medicine, NY tested the association of low 25(OH)D levels with all-cause, cancer, and cardiovascular disease (CVD) mortality in 13 331 nationally representative adults 20 years or older from the NHANES III linked mortality files.In patients on dialysis, therapy with vitamin D agents is associated with reduced mortality. Observational data suggests that low (25[OH]D) are associated with diabetes mellitus, hypertension, and cancers. However, whether low serum 25(OH)D levels are associated with mortality in the general population is unknown. Participant vitamin D levels were collected from 1988 through 1994, and individuals were passively followed for mortality through 2000. RESULTS: In cross-sectional multivariate analyses, increasing age, female sex, nonwhite race/ethnicity, diabetes, current smoking, and higher body mass index were all independently associated with higher odds of 25(OH)D deficiency (lowest quartile of 25(OH)D level, <17.8 ng/mL , while greater physical activity, vitamin D supplementation, and nonwinter season were inversely associated. During a median 8.7 years of follow-up, there were 1806 deaths, including 777 from CVD. In multivariate models , compared with the highest quartile, being in the lowest quartile (25[OH]D levels <17.8 ng/mL) was associated with a 26% increased rate of all-cause mortality (mortality rate ratio, 1.26; 95% CI, 1.08-1.46) and a population attributable risk of 3.1%. The lowest quartile of 25(OH)D level (<17.8 ng/mL) is independently associated with all-cause mortality in the general population.

Subst Abuse Rehabil. 2014 Dec 10;5:121-7. Effects of different doses of testosterone on gonadotropins, 25-hydroxyvitamin D3, and blood lipids in healthy men.Gårevik, Ekström ea. At the Karolinska Inst Sweden, Twenty-five healthy male volunteers aged 27-43 years were given 500 mg, 250 mg, and 125 mg of testosterone enanthate as single intramuscular doses. All doses investigated suppressed the LH and FSH concentrations in serum. LH remained suppressed 6 weeks after the 500 mg dose. These results indicate that testosterone has a more profound endocrine effect on the hypothalamic-pituitary-gonadal axis than was previously thought. There was no alteration in 25-hydroxyvitamin D3 levels after testosterone administration compared to baseline levels. The 250 and 500 mg doses induced decreased concentrations of ApoA1 and HDL, whereas the lowest dose (125 mg) did not have any effect on the lipid profile.

BoneKey Rep 2014:3:479:p1-8History of the discovery of vitamin D and its active metabolites Prof Hector deLuca graphically tells the story of the discovery of the lifesaving sun steroid cholecalciferol D3 between 1913 and its chemical formula in 1937, and then its’ functional chemistry through the 1970s. Until the preWW1 era, nutrition was blocked by false German dogma (von Liebig ea) that an adequate diet consisted of just 12% protein, 5% mineral, 10–30% fat and the remainder as carbohydrate. Such a diet – eg with polished rice, sugar and milled wheat- was shown to rapidly kill humans and animals ie without the essential micronutrient vitamins. .

Belief that this defined an adequate diet was to resurface in postWW2 Western capitalism in USA and UK through the twentieth century.

Then British, Continental and USA nutritional scientists started tearing that myth apart- and today we have the revelation that we need the ancient diet: just an adequate amount of first-class protein (but not soya); the bulk of needed nutritional calorie energy as natural fat (balanced omega 3: omega 6 and saturated medium chain triglycerides, but not transfats which are synthetic), with the balance of energy carbs and protein supplied by coloured veggies; supplying enough of the essential minerals, vitamins and marine oils.

But since most humans are no longer able to live off unpolluted unfarmed marine life or natural rotation-crop and grazed meat farming, but work indoors during daylight hours or, worse, disruptive night shifts, and city deathrates have risen steadily on the mythical low(but synthetic) fat, high carbs diet invented as dogma by Ancell Keys and his food factory cronies, the natural fat and -coloured-veggs -dominant diet rapidly re-establishes itself, with vigorous vit D3 and multivits to supplement the depleted and polluted fastfood chain.

update 22 Dec 2014: as the solstice rolls by, infections especially viral flourish north and south, from flu to gastro , HIV to ebola; HPV to HZV to childhood exanthems;

so more reason to aim for optimal growth, mental and physical health with the peak anabolic antidepressant energizing anticancer antiinfective steroid – cholecalciferol D3 – intake and levels. About 65 000iu a week (with my multivit-multimineral combo) puts my measured trough 25OHvit D bloodlevel at 92ng/ml with normal blood calcium. Women can live long without much androgen apart from frail bones, but not well without vigorous cholecalciferol D3 intake. Humans who live mostly bare mostly outdoors- us naked apes- most of the year closer to the equator make plenty of D3 from sunshine; but the darker our skins, the sooner vit D production shuts down; so most of us need vigorous D3 supplement costing perhaps US$6 a year retail. .

update 19 Nov 2014 when this column on vit D started 5 years ago, there were 46000 vit D entries on Pubmed- this has mushroomed 40% to 61000 (compared now to 46000 on vit A; to 53000 on vitamin C; 37000 on vitamin E; 17000 on vit K; and 133000 on all the 8 B vitamins ); whereas in 2009 there were 272500 entries on all vitamins– now up only 22% to 335 000. ie the papers on the secosteroid vitamin D have risen at double the rate of the vitamins.. (D3 C27H44O and D2 C28H44O, vs testosterone C19H28O2).

As the end-of-year solstice approaches, its time to review the crucial role of giving vigorous doses of vitamin D3, whether via non-burn sunshine, or via the correct lowpressure tanning bed, or directly as vitamin D3 (not vit D2) supplement as appropriate TOGETHER WITH A MULTINUTRIENT PLUS EXTRA MAGNESIUM AND VIT K2. . Ironically, dermatologists would recommend vit D supplement not suntan for what many consider the wrong reason- that suntanning does more harm than good, which it doesnt. :

3. Swanson, Barrett-Connor, ea USA & Belgium May 2014: In a cohort of older men, Higher 25(OH)D2 is associated with lower 25(OH)D3 and 1,25(OH)2D3, suggesting that vitamin D2 may decrease the availability of D3 and may not increase calcitriol.

5. Biancuzzo, Holick ea Boston Mass. 2013 Serum concentrations of 1,25-dihydroxyvitamin D2 and 1,25-dihydroxyvitamin D3 in response to vitamin D2 and vitamin D3 supplementationin healthy adults 18 to 79 years consuming 1000 IU vitamin D2 or vitamin D3 per day for 11 weeksat end of winter was analyzed. Of the adults, 82% were vitamin D insufficient (serum 25-hydroxyvitamin D [25(OH)D <30 ng/mL]) at the start of the study. Administration of vitamin D2 and vitamin D3 induced similar increases (from baseline ~20ng/ml 25OH vit D) in total 25(OH)D as well as in 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3, respectively. Compared with placebo and adjusting for baseline levels, 1000 IU daily of vitamin D2 was associated with a mean increase of 7.4 pg/mL (95% confidence interval, 4.4-10.3) in 1,25(OH)2D2, and decrease of 9.9 pg/mL (-15.8 to -4.0) in 1,25(OH)2D3. No such differences accompanied administration of 1000 IU daily of vitamin D3.

7. Sempos CT1, Picciano MF ea . USA J Clin Endocrinol Metab. 2013 Jul;98(7):3001-9..Is there a reverse J-shaped association between 25-hydroxyvitamin D and all-cause mortality? Results from the U.S. nationally representative NHANES.A reverse J-shaped association between serum 25-hydroxyvitamin D (25[OH]D) concentration and all-cause mortality was suggested in a 9-year follow-up (1991-2000) analysis of the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994). We repeated the analyses with 6 years additional follow-up in 15 099 participants aged ≥ 20 years with 3784 deaths, to evaluate whether the association persists through 15 years of follow-up. The reverse J-shaped association became stronger with longer follow-up and was not affected by excluding deaths within the first 3 years of follow-up. Similar results were found from both statistical approaches for levels <20 through 119 nmol/L. Adjusted RR (95% confidence interval [CI]) estimates for all levels <60 nmol/L were significantly >1 compared with the reference group. The nadir of risk was 81 nmol/L 32pg/mL (95% CI, 73-90 nmol/L 29-36pg/ml). The association appeared in men, women, adults ages 20 to 64 years, and non-Hispanic whites but was weaker in older adults. A reverse J-shaped association between serum 25(OH)D and all-cause mortality appears to be real. It is uncertain whether the association is causal.

11 Armas , Heaney ea.Creighton Univ Nebraska. J Clin Endocrinol Metab. 2004 ;89:5387-91. VitaminD2 is much less effective than vitaminD3 in humans.Vitamins D(2) and D(3) are generally considered equivalent in humans. Nevertheless, physicians commonly report equivocal responses to seemingly large doses of the only high-dose calciferol (vitaminD(2)) available in the U.S. market. Relative potencies of vitamins D(2) and D(3) were evaluated by administering single doses of 50,000 IU of the respective calciferols to 20 healthy male volunteers, following the serumvitaminD over 28 d.. The two calciferols produced similar rises in serum concentration, indicating equivalent absorption. Both produced similar initial rises in serum 25OHD over the first 3 d, but 25OHD continued to rise in the D(3)-treated subjects, peaking at 14 d, whereas serum 25OHD fell rapidly in the D(2)-treated subjects and was not different from baseline at 14 d. Area under the curve (AUC) to d 28 was 60 ng.d/ml for vitaminD(2) and 204 for vitaminD(3) (P < 0.002). Calculated AUC(infinity) indicated an even greater differential, with the relative potencies for D(3):D(2) being 9.5:1. VitaminD(2) potency is less than one third that of vitaminD(3). Physicians resorting to use of vitaminD(2) should beware of its markedly lower potency and shorter duration of action relative to vitaminD(3)

12 Trang, Vieth ea University of Toronto, Am J Clin Nutr.1998 . Evidence that vitaminD3 increases serum25-hydroxyvitaminD more efficiently than does vitaminD2. In all species tested, except humans, biological differences between vitamins D2 and D3 are accepted as fact. Subjects took 260 nmol (approximately 4000 IU)vitaminD2 (n=17) or vitaminD3 (n=55) daily for 14 d. With vitaminD3, mean (+/-SD) serum 25(OH)Dincreased from 41+/-18 nmol/L before to 65+/-17 nmol/L after treatment. With vitaminD2, the 25(OH)D concentration went from 434+/-18 nmol/L before to 57+/-13 nmol/L after. The increase in 25(OH)D with vitaminD3 was 23+/-16 nmol/L, or 1.7 times the increase obtained with vitaminD2 (14+/-11 nmol/L; P=0.03). There was an inverse relation between the increase in 25(OH)D and the initial 25(OH)D concentration. In the highest tertile [25(OH)D >49 nmol/L] the mean increase in 25(OH)D was 13.3 nmol/L (P < 0.03 for comparison with each lower tertile). Although the 1.7-times greater efficacy for vitaminD3 shown here may seem small, it is more than what others have shown for 25(OH)D increases when comparing 2-fold differences in vitaminD3 dose. The assumption that vitamins D2 and D3 have equal nutritional value is probably wrong and should be reconsidered.

13. Hymøller L1, Jensen SK.Denmark J Dairy Sci. 2011;94:3462-6. Vitamin D₂ impairs utilization of vitamin D₃ in high-yielding dairy cows in a cross-over supplementation regimen. D(3) given after D(2) is less efficient at increasing the plasma status of 25(OH)D(3) than D(3) given without previous D(2) administration.

A Vitamin D Expert’s Take on the Latest Warning to Stay Out of the Sun to Avoid Skin Cancer

By Dr. Mercola 16/11/2014The US Surgeon General recently came out with a warning on skin cancer,1 claiming that the sun is dangerous and that you need to stay away out of it.

pioneer Dr. John Cannell, founder of the Vitamin D Council, has dedicated a large part of his professional career to the study of vitamin D and its health benefits, and he has a warning of his own to those who take this narrow-minded advice to heart.

It’s worth noting that the acting Surgeon General, Boris Lushniak, is a dermatologist. And of all the medical specialties out there, dermatologists are clearly the most biased against sun exposure, & as a result, against vitamin D.

This isn’t surprising, since they primarily see the ill effects of sun overexposure. But in taking an overly narrow view, the advice to avoid sun exposure as much as possible can have equally if not greater adverse health effects. The Connection Between Sun Exposure and Skin Cancer Unquestionably, UV radiation can be dangerous; it can increase your risk for certain skin cancers such as squamous cell, basal cell, and melanoma. But there are significant differences even between these cancers, and appropriate sun exposure may actually be more beneficial than detrimental in some cases. Dr. Cannell explains:

“Squamous cell carcinoma is clearly associated with chronic sun exposure. It is more common on the face, the hands, and the scalp.

It is related to radiation burden over your lifetime, and together with basal cell carcinoma, which is sort of intermediate, it accounts for approximately 1,500 deaths a year in the United States…

Basal cell is sort of intermediate. There are studies showing that it is associated with chronic sun exposure, and there are studies showing that it’s not associated with chronic sun exposure.

And then there’s melanoma, which is responsible for almost 9,000 deaths a year and is the deadly skin cancer that is feared. The relationship that melanoma has with the sun is quite complicated.

It is clearly associated with sunburn, especially sunburns when you’re young (that’s incontrovertible) or sunburns in a sun tanning bed.”

However, there are at least two studies showing that melanoma is more common in indoor workers than outdoor workers. And the most likely places for melanoma to appear are actually NOT the face and the hands like squamous cell carcinoma, but rather the lower back and the upper leg—areas that are usually not chronically sun-exposed.

According to Dr. Cannell, there’s a vocal minority in the dermatological community that thinks the emphasis dermatologists have on avoiding sun exposure is wrong, because while sunburn is a risk factor, chronic sun exposure is not.

“A number of studies show that chronic sun exposure is related to melanoma, but they don’t separate out the sunburns, which is very hard to do because you have to do that by memory,” Dr. Cannell says. Two Decades-Long Study Finds Sun Avoidance Doubles Risk of Death Dr. Cannell notes a recent study2 done in Sweden, which followed nearly 30,000 middle-aged to older women for up to 20 years. The average follow-up was 15 years.

At the outset, they asked a number of questions about sun exposure, such as: Do you sunbathe? Do you take vacations in sunny areas in the winter? Do you garden with short sleeves and shorts? And, do you use sunbeds?

What they found, and this appears to be the only study of this kind, is that the women who avoided the sun were twice as likely to die over the course of the study. The researchers attributed this finding to a vitamin D mechanism.

What this study actually shows is that chronic sun exposure appears to be associated with less mortality. It’s also the first study to show that women who use tanning beds live longer than those who don’t.

This is in direct conflict to what almost every dermatologist will say, including the Surgeon General. It’s unfortunate, but the danger of almost any specialist is that they don’t take the broader perspective.

What the Surgeon General and almost every other dermatologist fail to take into account is the overall mortality, which is referenced in this recent study. Risk-Benefit Analysis In addition to this study, dozens of others document the benefits of appropriate sun exposure. This includes a reduced risk of about 16 different cancers of Dr. Garland’s studies suggest this reduction is close to 50 percent.

So many hundreds of thousands of people are put at risk from other cancers as opposed to 10,000 people who are dying from skin cancer caused by sunburn. It’s really a matter of making an educated risk-benefit analysis.

“When you do a risk-benefit analysis and you look at all the data we have, the risk in my opinion appears to be in those who avoid the sun,” Dr. Cannell says.

“Now, if you avoid the sun, your risk for non-melanoma skin cancer goes down. That’s clear. But if you look at studies of either latitude or of 25-hydroxyvitamin D levels in relation to cancer, you find this inverse relationship: the higher the vitamin D level, the lower the internal cancer rate.”

Dr. William Grant of Sunlight, Nutrition, and Health Research Center (SUNARC) estimates that if everyone in the United States had a vitamin D level of 40 nanograms per milliliter (ng/ml), it would save approximately 150,000 lives a year.3

That’s 100 times the rate of squamous cell cancers, which are the only ones that are definitively linked to UV exposure. In Canada alone, it is estimated that 37,000 lives a year are lost due to vitamin D deficiency.4Also, use of sunscreen has risen in the last 30 years, so if dermatologists were correct, there should be a decrease in stage 1 melanoma. But there’s not. As sunscreen use increased, stage 1 melanoma diagnosis increased…

“It’s thought that by blocking out UVB, patients are able to stay out in the sun longer than they would have otherwise and expose themselves to the more dangerous, or at least potentially dangerous, UVA radiation that’s in the sunshine,” Dr. Cannell says. “What we recommend is what’s called safe, sensible sun exposures. The Australian Cancer Council now recommends the same thing. I think in England there’s now a change in their recommendation from strict sun avoidance to some safe, sensible sun exposure. There are some movements in large organizations to realize that safe, sensible sun exposure is a healthy thing.”

How Much Sun Exposure Is Sensible? On its website, Cancer Research UK reports that “by enjoying the sun safely and avoiding sunburn, people can reduce their risk of skin cancer and enjoy the beneficial effects of the sun.” Cancer Research UK’s sun advice is endorsed by the British Association of Dermatologists, Cancer Research UK, Diabetes UK, the Multiple Sclerosis Society, the National Heart Forum, the National Osteoporosis Society, and the Primary Care Dermatology Society. The UK National Health Service5 also recommends sensible, individualized sun exposure to help optimize vitamin D.

It’s important to recognize is how quickly sunlight can make vitamin D in the skin. You don’t need to be outside for hours on end. But you do need more than just a few minutes of sun on your face and arms. According to Dr. Cannell, sunbathing at solar noon in the summer, at most latitudes in the United States you will make between 5,000-10,000 international units (IUs) of vitamin D within 30 minutes.

“You can ask yourself why nature would evolve a mechanism that made so much vitamin D so quickly,” Dr. Cannell says. “When I thought about that question, the only answer I could come up with is nature did it for a good reason. The organism needs vitamin D, so the system in the skin evolved to make it very quickly upon exposure to sunlight.

We recommend full-body sun exposure for up to anywhere from a few minutes to 30 minutes every day. On those days when you cannot get a full-body sun exposure, we recommend a vitamin D supplement or sensible exposure in a low-pressure UVB bed.”

If you’re getting regular sun exposure, I think the need for an oral supplement is really minimal to non-existent. When you swallow a pill, there’s no self-regulating ability. Your body doesn’t have an ability to selectively limit its absorption. But your skin has the ability to control how much vitamin D is being produced based on how much is in your blood.

I personally have not taken oral vitamin D for five years and my level runs from 50-70 g/ml. Lifeguards, roofers, and gardeners who work with their shirt off, all tend to have levels between 40 and 80 ng/ml in the summer. This also brings up an interesting question about the difference between normal and natural. Normal vitamin D levels are an average of what indoor workers have in both winter and summer. Natural are levels of a population with widespread sun exposure. The latter is going to be closer to ideal, or optimal.

References for establishment of optimal levelsThere are also other reasons to strive for sun exposure rather than swallowing a pill. As noted by Dr. Cannell, aside from producing vitamin D, sunlight also affects nitric acid levels and endorphins in the skin. Researchers at the University of Wisconsin recently discovered that there may be a system at 311 nanometers that is separate from the vitamin D system (which is at 298 nanometers), and that there may be an entirely new undiscovered biochemical system in the skin that makes yet another substance, besides vitamin D. Time will tell what comes out of that research, but there are indications that sunlight may be responsible for other biological processes that are unrelated to vitamin D production.

Dr. Cannell’s Recommendation on Tanning Beds There are basically two
types of tanning beds:

1. High-pressure UVA beds. They tan you the quickest because it’s UVA that tans the skin. They contain only a limited UVB spectrum, and will therefore give you color but not much vitamin D

Low-pressure beds, which contain less UVB than sunlight at most latitudes, but still contain a significant amount of UVB. These are the beds Dr. Cannell recommends, provided you’re using a sensible approach that avoids sunburns. It’s important to realize that you can easily get burned after only a couple or a few minutes when using a tanning bed

Another important factor when selecting a tanning bed is the type of ballast it employs, to avoid excessive electromagnetic field (EMF) exposure. Most tanning units use magnetic ballasts to generate light. These magnetic ballasts are well known sources of EMF fields that can contribute to cancer. If you hear a loud buzzing noise while in a tanning bed, it has a magnetic ballast system. I strongly recommend you avoid magnetic ballast beds, and restrict your use of tanning beds to those that use electronic ballasts.

On days you cannot get either regular sun exposure or use of a tanning bed, Dr. Cannell suggests taking 5,000 IUs of vitamin D3. Other vitamin D experts recommend similar amounts. It’s worth noting that, according to the federal government’s Food and Nutrition Board (FNB), the no observed adverse effects level (NOAEL) of vitamin D is 10,000 IUs a day. This means there has never been a replicated reliable study showing that 10,000 units a day is in any way detrimental.

Many individuals who have reported side effects from taking high doses of oral vitamin D have noticed that when they supplemented with magnesium, they were able to tolerate the high oral doses of vitamin D. Dr. Carolyn Dean has written in her book, The Magnesium Miracle, that she has seen this so many times that she doesn’t advise taking more than 2,000 units of vitamin D without magnesium supplementation. Be sure to also have an adequate amount of vitamin K2 along with D to slow the progression of arterial calcification. Remember though that the best form of vitamin D is the one your body produces when it is exposed to sunlight that has sufficient amounts of UVB.

Five Tips to Get an Appropriate, Sensible Amount of Sun Again, sunshine offers substantial health benefits, including vitamin D production, but you do need to exercise a few simple precautions to protect yourself from overexposure. Virtually all of the harm from sun exposure is related to sunburn. Here are my top five tanning tips: * Expose large amounts of your skin (at least 40 percent of your body) to sunlight for short periods daily. Optimizing your vitamin D levels may reduce your risk of as many as 16 different types of cancer, including pancreatic, lung, ovarian, breast, prostate, and skin cancers. If using a sunscreen, give your body a chance to produce vitamin D before you apply it. *When you’ll be in the sun for longer periods, cover up with clothing, a hat, or shade (either natural or shade you create using an umbrella). *Consider the use of an “internal sunscreen” like astaxanthin to gain additional sun protection. Astaxanthin is a potent antioxidant (and pigment) produced by marine algae in response to their exposure to UV light. Typically, it takes several weeks of daily supplementation to saturate your body’s tissues enough to provide protection. *Consuming a healthy diet full of natural antioxidants is another useful strategy to help avoid sun damage. Fresh, raw, unprocessed vegetables and fruits deliver the nutrients that your body needs to maintain a healthy balance of omega-6 and omega-3 oils in your skin, which is your first line of defense against sunburn. Vegetables also provide your body with an abundance of powerful antioxidants that will help you fight the free radicals caused by sun damage that can lead to burns and cancer.

How Vitamin D Performance Testing Can Help Optimize Your Health A robust and growing body of research clearly shows that vitamin D is absolutely critical for good health and disease prevention. Vitamin D affects your DNA through vitamin D receptors (VDRs), which bind to specific locations of the human genome. Scientists have identified nearly 3,000 genes that are influenced by vitamin D levels, and vitamin D receptors have been found throughout the human body.

14 Oct 2014 update: MORE ON OPTIMAL VITAMIN D3 DOSE, AND THE DIFFICULTY OF ACHIEVING CLINICAL OVERDOSE: Four new reports highlight how difficult, and important it is to achieve adequate optimal bloodlevels of vitamin D with vigorous vitamin D3 supplements, let alone overdose with any significant adversity: note three used the recommended vitamin D3, not the long-condemned mislabeled Lennons/Aspen vitamin D2 (which is misleadingly labelled “caciferol” without disclosing that it is D2 not D3). Even a single 2 million iu overdose of vit D3 in nonagenarians had no adverse effect-since the bloodlevel was back to zero by 3 weeks, thats above 100 000iu/day on average….

van den Ouweland , Vollaard ea Nijmegen, The Netherlands in BMC Pharmacol Toxicol. 2014 Sep 30 describe Pharmacokinetics and safety issues of an accidental oral overdose of 2,000,000 IU of vitamin D3 in two nonagenarian nursing home patients: a case report. Oral overdose of 2,000,000 IU of vitamin D3 in two nonnagenarian nursing home patients was monitored from 1 hr up to 3 months . Peak blood 25(OH)D3 concentrations were observed 8 days after intake (210 and 162ng/mL, respectively (ref: 20-80 ng/mL), followed by a rapid decrease to undetectable levels after day 14. Remarkably, plasma calcium levels increased only slightly up to 2.68 and 2.73 mmol/L, respectively (ref: 2.20-2.65 mmol/L) between 1 and 14 days after intake,; phosphate and creatinine levels remained within reference range. No adverse clinical symptoms were noted. CONCLUSION:A single massive oral dose of 2,000,000 IU of vitamin D3 does not cause clinical toxicity requiring hospitalization. Toxicity in the long term cannot be excluded as annual doses of 500,000 IU of vitamin D3 for several years have shown an increase in the risk of fractures. This means that plasma calcium levels may not be a sensitive measure of vitamin D toxicity in the long term in the case of a single high overdose.

As previously reported, to avoid dehydration stones and vascular calcification – especially in hot dry climates – , the precautions with vigorous vit D3 are to add some vit K2 and magnesium to the supplement, and maintain good water intake .

The fourth current paper, from Morocco, reports inexplicable use of dangerous massive dose of vit D2 in neonates- amounting to about 120 000iu/kg ie about 12 times the maximum adult dose reported : Hmami , Bouharrou ea Morocco University, Arch Pediatr. 2014 Oct;21:1115-9. [Overdose or hypersensitivity to vitamin DVitamin D intoxication with severe hypercalcemia is rare in the neonatal and infancy period. 9 babies between ages of 25 and 105 days were admitted for treatment of severe dehydration 8 to 15% with hypercalcemia, with preserved diuresis and loss weight between 100 and 1100 gm secondary to taking 600,000 units of vitamin D (Sterogyl(®). The pregnancies & deliveries were normal. Clinical signs were dominated by weight loss, vomiting, and fever. The vitamin D values in nine patients were toxic (mean 220: 139 – 300 ng/mL, ; normal >20ng/mL; toxicity if >100ng/mL). Nephrocalcinosis was shown in seven patients. DNA study in eight patients, did not reveal a mutation of the vitamin D 24-hydroxylase gene (CYP24A1). Treatment consisted of intravenous rehydration with diuretics and corticosteroids. Serum calcium returned to normal range within 4-50 days, with weight gain progressively over the following weeks. The follow-up (2 years for the oldest case) showed persistence of nephrocalcinosis. Genetic susceptibility and metabolic differences appear to modulate the threshold of vitamin D toxicity. However, respect for recommended doses, recognized as safe in a large study population, reduces the risk of toxicity.

VITAMIN D3 DOSE:We get excellent results in outpatient adults with loading oral dose of vit D3 of about 200 000 to 400 000iu depending on illness severity and body mass; then pro rata about 50 000iu per week till better, tapering to fortnightly when well; pro rata in kids. We monitor calcium and 25OH vitamin D3 levels occasionally if affordable – but with the tapering regime, and published data, do not see or expect hypercalcemic problems from a mean conservative weekly maintenance dose of about 3500iu/d longterm, with predicted bloodlevel of 25OHvitD of about 35-40ng/ml. As a senior with average chronic dis-ease load, I take ~63 000iu vit D3 weekly, but double it occasionally if I do get a bad cold; so I never miss a day’s work; recent stress-related shingles (2nd attack in 30 years) was just a nuisance, settled in 3 weeks with this regime plus multigrams of buffered vit C a day; oral lysine and alphalipoic acid each about 1/2 gm/day; and for a few days some weak steroid and humic acid cream topically for the neuritis and blistering, which has already healed to almost invisible. This week at a family practice clinic I saw two successive women with shingles – now a frequent occurrence, even without HIV…

Khan in Toronto in OHDM this September describes a ~60yr old man with tongue cancer who was treated inter alia with Vit D3 10 000iu a day; after a year his 25oH vitD level was ~106ng/ml, when his dose was halved; his dose response bore out the general experience that at average adult mass, vit D level rises by about 10ng/ml for every 1000iu vit D3 per day or pro rata dose weekly etc eg 50 000iu/wk or 100 000iu fortnightly may give average vit D level of ~70ng/ml. .

Singh & Bonham 2014 at Kansas University describe A Predictive Equation to Guide Vitamin D Replacement Dose in Patients. “The recommended daily allowance for vitamin D is grossly inadequate for correcting low serum concentrations of 25-hydroxyvitamin D in many adult patients. In their population (average BMI 31.5) ,about 5000 IU vitamin D3/day is usually needed to correct deficiency, and the maintenance dose should be ≥2000 IU/day. The required dose may be calculated from the predictive equations specific for ambulatory and nursing home patients” A BMI of 31.5kg at a mean height of about 1.7m gives a mean weight of 91kg, which at the consensus daily vit D3 dose of 80iu/kg/d totals ~7100iu/d or 50 000iu/wk- perhaps a reasonable maintenance dose for winter, half that in summer if reasonable weekly sun exposure. .

29 Sept 2014: As detailed elsewhere in this column, there is at least 70 years of strong experience worldwide that all microorganism infections are greatly diminished by natural prevention (not synthetic vaccines loaded with toxic heavy metals and allergenics eg egg) , and easily treated ie thrown off, with vigorous immune-boosting supplements: (mega)grams a day of vitamin C or as kgs/day of fresh produce; vitamin D3 80+ iu/kg/d to >10 000iu/d ie 300 000 to 600 000iu loading dose; then +-50 000iu/wk, plus plenty of skin exposure to sunshine; iodine; zinc; selenium; silver; the other vitamins; Ecchinacea etc. This applies both to acute and chronic infections and degenerative conditions.

To be used in highrisk cases eg MERS, AIDS, ebola etc: The landmark trial Effect of High-Dose Vitamin D3 on Hospital Length of Stay in Critically Ill Patients With Vitamin D Deficiency– The VITdAL-ICU Randomized Clinical Trial by Amrein, Dobnig ea , published today in JAMA from Austrian hospitals is most encouraging about the immense value of vigorous dose and bloodlevels of vitamin D3 against all types of severe disease. The dose used in this trial (loading dose 540 000iu =~18000iu/d 1st month, but averaging only ~8000iu/d in the first 3mo) did not achieve vigorous vit D bloodlevel, presumably because the loading dose of vit D3 in oil (540 000iu) was given by tube into the stomachs of critically ill patients; it would have better been given by transdermal injection, or else a much higher loading gastric dose given so as to speedily achieve a bloodlevel of around 70 (60 to 80) instead of half of this that was achieved in the crucial first few weeks . “from May 2010 through September 2012 at 5 ICUs the trial recruited 492 medical (60%) and surgical (40%) critically ill adult white patients , 35% women, BMI mean 27, mean age 64.6 years (SD, 14.7) with vitamin D deficiency (≤20 ng/mL) assigned to receive either vitamin D3540 000 IU, or placebo given orally or via nasogastric tube; ; followed by monthly maintenance doses of 90 000 IU for 5 months- ie= about 18000iu/day for the first mo, then 90 000iu mthly ie only 3000iu/d. . RESULT: on placebo the 25hydroxyvit D3 level doubled from 13 at baseline to 17 at a month to 26ng/ml at 6mo.. By contrast, on vit D3 supplement it doubled to 34 at days 3 and 7 and day 28, but up to 46 at 6 months ie only 80% higher than the control group – thus 1/3 to 1/2 of the optimal target; with this, where 100% of patients were below 25OHvitD at baseline ie on admission to ICU, by 7 days, 87% were still in this bracket and none above 60ng/ml on placebo vs 25% below 20 and 13% above 60 on vit D3; and by 6mo 35% were still that low on placebo, vs 5% at that low, but 22% above 60 on vit D3.So it is not surprising thatMedian hospital stay 20 days was not significantly different between groups Hospital mortality and 6-month mortality were also not significantly different (hospital mortality: 28% for vitamin D3 vs 35% for placebo; hazard ratio [HR], 0.81 P = .18; 6-month mortality: 35.0% for vitamin D3 vs 42.9% for placebo; HR 0.78 P = .09). For the severe vitamin D deficiency subgroup analysis (n = 200), length of hospital stay was not significantly different between the 2 study groups: 19.5 days. Hospital mortality was significantly 40% lower with 28 deaths among 98 patients (28.6% ) for vitamin D3 compared with 47 deaths among 102 patients (46.1% ) for placebo (HR, 0.56 P for interaction = .04), but not 6-month mortality (34.7%] for vitamin D3 vs 50.0% for placebo- ie 31% lower; HR, 0.60, P for interaction = .12). No serious adverse events were observed. The highest 25-hydroxyvitamin D levels measured were 107 ng/mL on day 7 and 106 ng/mL at month 6- well below the theoretical minimum toxic threshold of 150 or 250ng/ml..”

As Salahuddin ea note, the good results in Pakistan in only 3 months with vigorous INITIAL dose vit D3 contrasts with Two recently published large randomised, controlled trials of conservative vitamin D3 over months that achieved far lower blood vitamin D levels found no difference in clinical outcomes or mortality after 400,000IU of 25-hydroxyvitamin D3 or placebo were given by Martineau ea in London, UK to 146 pulmonary TB patients – where mean (trough or midpoint) vit D level (after 100 000iu vitamin D(3) or placebo at baseline and 14, 28, and 42 days after starting standard tuberculosis treatment) – was surprisingly only 40ng/ml at 56days – ie after a mean of 7000iu/d by 56 days, vs 10ng/ml on placebo)- less than half of the bloodlevel achieved on vit D3 in the Pakistan trial.

So the Austrian ICU patients would undoubtedly have done much better if given more effective (ie in critically ill pts intramuscularly imi or subcutaneously) loading dose like the Salhuddin trial did.

TIME To SWOP FROM MISNAMED “STRONG CALCIFEROL” VIT D2 TO THE REAL VIT D3: as the winter solstice approaches here, with fierce weather linking to the expected influenza-like outbreak (while the MERS-CoV outbreak abates with summer in the severely vitamin D deficient Saudi Arabians), a new major study shows the supremacy of vitamin D3 for supplementation, and confirms that vitamin D2 benefit if any is so mediocre as to be unethical..

Its sad that despite the strong evidence against using vitamin D2 supplement discussed last year, it seems no one acted on it despite the confirmatory paper from Bergen of last September.

Thus vit D3 is again confirmed as four times as potent as D2. But crucially, that giving vit D2 may actually SUPPRESS the optimal serum vit D3 level.

We health professionals with our highly vulnerable populations in South Africa and worldwide (epidemic/endemic HIV, TB, cancer, drug addiction, MERS-CoV, asthma, diabetes, cardiovascular, malnutrition, alcoholism and violence) therefore surely have no choice but to swop promptly from prescribing vit D2 “Strong Calciferol” (a dangerous misnomer) to prescribing vitamin D3 at vigorous dose (with if possible occasional blood level check of 25OHvit D3)- at a trivial imported and distributed cost (100cws) to South African state clinics of perhaps<1/4 of the cost of D2 eg R1 per patient per month for a conservative 100 000iu monthly (ie after an appropriate germicidal loading dose of eg 3000 iu/kg) if not the more realistic dose double that- still at only eg US$0.2 a month.

Health Authorities everywhere have an obligation to enforce the use of vitamin D3 and not vitamin D2 globally ..

update 3 Sept 2014: while the MERS outbreak in Arabia may at last be dying down, real highly infections plagues eg ebola malaria cholera typhoid, MRSA, TB and HIV etc continue rampant, maiming and killing even more than the manmade wars raging on some continents. .

So it is ironic – or typical of the couldnt-care-less greedy politicians and potentates who run the world- that the medical authorities they employ worldwide apparently continue to ignore the dramatic benefits of at least safe antimicrobial supplements like multivite, zinc, iodine, selenium, and especially vigorous dose vitamin D3 at negligible cost, and highdose buffered vitamin C to tolerance, and colloidal silver.

We quote above trials and evidence that oral vit D2 may be actually harmful, that it is vit D3 in vigorous dose that is needed to at least treble if not quadruple the blood vit D level from the usual deficient levels we find, to between 60 and 100ng/ml during illness. Unfortunately locally this is not only not grasped, but also the vit D assay kit being used by private laboratories measures only total 25OHvit D level, not the needed active 25OH vit D3 level plus the potentially harmful (vitD receptor-blocking ) 25OHvit D2. This is a crucial omission which has been corrected by eg the Mayo Clini Lab, which routinely reports both D3 and D2 levels.

In the person not on vit D supplements, the mediocre ie insufficient total vit D level may mask that the crucial vit D3 level is actually seriously low- deficient. In the person on vigorous vit D2 supplement (the spuriously named “strong calciferol” 50 000iu tab no longer prescribed in USA but commonly in RSA, that neglects to state it is D2 not D3), the total 25OH vit D assay will be even more misleading if the level is well up, without the unwary being informed that it is harmful D2 that is elevated, and blocking the needed vit D3 level that the D2 is suppressing.

15 June 2014 CRUCIAL EFFECTIVE VITAMIN D3 DOSING: A major new metaanalysis of the benefit ofVitamin D3 and RespiratoryTractInfections RTIin PLOS 2013 at Sweden’s Karolinska Institute Bergman ea showed that in the 11 relevant trials (published between 2007 and 2012 ie done through the first decade of this century) using vit D3, “Overall, vitamin D showed a protective effect against RTI (OR, 0.64; 95% CI, 0.49 to 0.84). And the average vit D level at baseline was only 24ng/ml, but with the mediocre vit D3 doses used then of average 2000iu/d (300 – 4000iu/day) given for between 7wks and 3 yrs, the average bloodlevel achieved on replacement was only 50% higher at 36ng/ml”.

This confirms more direct experience with higher doses that blood level increment, and benefit, is proportionate to vit D3 dose, at least up to the proven speculative safe upper dose of at least 10 000iu/day (whereas the proven safe longterm daily dose is up to 50 000iu/day). “More important, the protective effect was larger in studies using once-daily dosing compared to eg monthly bolus doses (OR=0.51 vs OR=0.86, p=0.01)”. This concurs with our experience of major benefit against respiratory infection that is based on published studies giving a loading month’s dose of about 80-100 iu/kg/day ie ~3000iu/kg; then that monthly dose split conservatively eg 50 000iu every week or two depending on mass, and severity of ill-health; to a more successful blood-level of 60 to 100ng/ml.

These recent studies force us to conclude that bad weather, and bad prevalent respiratory viruses, and especially with major acute, or chronic illness as in those with or at risk of serious infections eg major trauma or sepsis, MERS-CoV, Ebola, malaria, cholera, cancer, diabetics, smokers, asthmatics, bronchitics, AIDS-TB., pneumonia and old age sufferers, and especially hospital, laboratory and clinic- health workers- we should give a loading dose of about 4000iu/kg, then 10 000 iu/d for an average 70kg adult, or 50 000iu every 5 days, or more simply 75000iu (about 1.5ml of 100cws vit D3 powder) weekly; or at a stretch, 300000 if not 400 000iu monthly. . As the common imported powder concentrate is 100 000 iu / Gm ie per 2 ml, it is simple to take the slightly sweetish powder up to 2 or more 4 ml teaspoons ie 200 000 -400 000 iu on the tongue.

The majority of residents of developed countries now live urbanised with mechanized transport, do not live and work / walk all day stripped in the sun. The poor malnourished peasants live crowded in ghettoes , and the poorest are generally the darkest skinned and therefore make the least vitamin D3. So with rare exceptions, everyone needs the vigorous vitamin D 3 doses discussed above.

But at the prevalent bulk vit D3 powder price of at most about $0,o2 per 100 ooo iu, at a mean population age of around 20 to 25 yrs -outside Europe- it would cost a country of eg 50 million people perhaps $o.5 per head per year ie conservatively $25 million a year to prevent > 90% of common illnesses including drugging and violence consequences. Of course no government can tolerate such massive loss of jobs and taxes in a decimated disease industry that turns over $ trillions annually – up to 18 % of national budgets. So it’s up to individual adults, especially householders, educators and employees , to see that the cheapest cure- all after clean water – vitamin D3 – is recommended and freely available.

We health professionals with our highly vulnerable populations in South Africa and worldwide (epidemic/endemic HIV, TB, cancer, drug addiction, MERS-CoV, asthma, diabetes, cardiovascular, malnutrition, alcoholism and violence) therefore surely have no choice but to swop promptly from prescribing vit D2 “Strong Calciferol” (a dangerous misnomer) to prescribing vitamin D3 at vigorous dose (with if possible occasional blood level check of 25OHvit D3)- at a trivial imported and distributed cost (100cws) to South African state clinics of perhaps<1/4 of the cost of D2 eg R1 per patient per month for a conservative 100 000iu monthly (ie after an appropriate germicidal loading dose of eg 3000 iu/kg) if not the more realistic dose double that- still at only eg US$0.2 a month.

Health Authorities everywhere have an obligation to enforce the use of vitamin D3 and not vitamin D2 globally ..

Queries and rebuttals all over the world are questioning the negative French (Autier ea) Vitamin D status and ill health: a systematic review published last month by the UK Lancet Low serum concentrations of 25-hydroxyvitamin D (25[OH]D) have been associated with many non-skeletal disorders. However, whether low 25(OH)D is the cause or result of ill health is not known. We did a systematic search of prospective and intervention studies that assessed the effect of 25(OH)D concentrations on non-skeletal health outcomes in individuals aged 18 years or older. We identified 290 prospective cohort studies (279 on disease occurrence or mortality, and 11 on cancer characteristics or survival), and 172 randomised trials of major health outcomes and of physiological parameters related to disease risk or inflammatory status. Investigators of most prospective studies reported moderate to strong inverse associations between 25(OH)D concentrations and cardiovascular diseases, serum lipid concentrations, inflammation, glucose metabolism disorders, weight gain, infectious diseases, multiple sclerosis, mood disorders, declining cognitive function, impaired physical functioning, and all-cause mortality. High 25(OH)D concentrations were not associated with a lower risk of cancer, except colorectal cancer. Results from intervention studies did not show an effect of vitamin D supplementation on disease occurrence, including colorectal cancer. In 34 intervention studies including 2805 individuals with mean 25(OH)D concentration lower than 50 nmol/L at baseline supplementation with 50 μg per day or more did not show better results. Supplementation in elderly people (mainly women) with 20 μg vitamin D per day seemed to slightly reduce all-cause mortality. The discrepancy between observational and intervention studies suggests that low 25(OH)D is a marker of ill health. Inflammatory processes involved in disease occurrence and clinical course would reduce 25(OH)D, which would explain why low vitamin D status is reported in a wide range of disorders. In elderly people, restoration of vitamin D deficits due to ageing and lifestyle changes induced by ill health could explain why low-dose supplementation leads to slight gains in survival.

Ongoing randomised clinical trials assessing the ability of vitamin D supplementation to reduce the risk of several non-skeletal disorders involve a population larger than that of Cambridge, UK, and will cost millions of research dollars. VITAL, for example, will enroll 20 000 participants and has US$22 million in funding. This vast investment of effort by patients, researchers, and funders is laudable, as it is almost certain that it will be sufficient to answer a question that has long kept the medical community in the dark.

Vitamin D first became a medical success story when its importance in bone health and calcium homoeostasis was proven decades ago. Since then, epidemiological evidence has been accumulating to support a role for vitamin D in the protection of individuals from various non-skeletal disorders including cancer, cardiovascular diseases, autoimmune and inflammatory diseases, dementia, and diabetes; it might also reduce all- cause mortality. Many of these studies show a strong association between low vitamin D concentrations anddisease. However, the results of myriad recent small randomised controlled trials are almost unanimous in concluding that vitamin D supplementation provides protection from few, if any, of these outcomes.

Vitamin D is a steroid hormone with pleiotropic and tissue-specific effects owing to the wide expression of the nuclear vitamin D receptor in many different tissues,and the many genes that are targeted by its actions. In the skeletal system, vitamin D promotes healthy development and remodelling of bone. In other tissues, vitamin D is postulated to mediate potentially beneficial effects via a wide variety of mechanisms: some evidence suggests that it exerts anticancer activity by limiting hyperproliferation of certain cell types, that it promotesmetabolic health by regulating lipid metabolism in adipocytes, and that it limits autoimmunity bysuppressing inappropriate immune responses. In a systematic review in The Lancet Diabetes & Endocrinology editorial , Philippe Autier and colleagues discuss a large number of observational studies suggesting That high serum concentrations of vitamin D might be protective.

For example, those with high vitamin D had decreased risk of cardiovascular events by up to 58%), diabetes (by up to 38%), colorectal cancer (by up to 33%), and all-cause mortality (by up to 29%). However, they also compare these findings with the results of randomised clinical trials, which reveal a very different picture: no reduction in risk was found, even in trials involving adequate supplementation of participants with lowvitamin D levels at baseline (less than 50 nmol/L). Autier and colleagues also did a new meta-analysis of 16 trials that assessed the effects of vitamin D supplementation on blood HbA1c, a biomarker mainly used for monitoring disorders of glucose metabolism.

Although type 2 diabetes is associated with low vitamin D, the results show that vitamin D supplementation does not reduce HbA1c

. Thus, it looks increasingly likely that low vitamin D is not a cause but a consequence of ill health.

Despite the growing body of evidence indicating that vitamin D is unlikely to prevent non-skeletal disorders, there is strong support for its use from many prominent members of the research community, which is fuelled by the relatively low toxicity of vitamin D, the glimmer of positivity from some trials,and the large body of evidence from prospective observational studies. For those who ‘believe’, the lack of benefi t found in most trials completed thus far can be attributed to issues including inadequate supplementation, testing of a population not sufficiently vitamin D deficient at baseline, incorrect

formulation, underpowering, or insufficient follow-up. Vitamin D might not be safe in all settings, however.

Supplementing at high doses could cause harm in people with already high concentrations of serum vitamin D, particularly in those with liver, kidney, or vascular problems. This is a concern, given the large number of people taking vitamin D supplements (up to 50% of adults in the USA).

Large clinical trials to assess the effects of vitamin D on non-skeletal health outcomes are therefore justified. It would be a real boon to patients if the results are positive, but unless effect sizes for clinically important outcomes are large, the results will only confirm the neutral effect reported by most clinical trials thus far. Although this investment might therefore have little effect on current guidelines, the results will at least allow the research community to move on.

This French review of Vitamin D is the sort of tactic regularly concocted by Big Pharma and the Disease Industry for the media, to discourage patients and doctors from taking/prescribing effective doses of supplements (beyond a lowdose multivite a day), instead force them to take Big Pharma poisons- synthetic new risky designer drugs- like antibiotics, antipain, anticancer, anticholesterol, antiosteoporosis, antiplatelet,antihypertensive, vaccines, antiflu, – to make massive profits for the Disease Industry, but not address or cure the deficiency causes of disease. At the behest of Big Pharma like Roche, their lobbyists the FDA, the European Medicines Authority and the UK NHS are trying to push through legislation that will make anything but lowdose multisupplements available to the public solely on doctors’ prescription.

Meanwhile, Big Pharma companies are paying fines of over $10 billion a year for promoting their snakeoil prescription designer drugs by fraud, when these drugs are allowed to be registered for chronic use after small trials of only 6 to 12 weeks, and the researchers who publish the trials for megadollar fees are regularly caught out, fired but rarely jailed. …… The Big Pharma guys simply bill the cost of the fines into their marketing expenses- their bosses, and the politicians they buy off, are too big to jail… Regulators then allow the drugs to be prescribed for years until enough patients sicken and die for there to be an uproar and cancellation- as happened recently with Prot(e)os the synthetic ranelate ‘osteoporosis’ snakeoil;. Now a top Dutch researcher has been fired for falsifying trials to promote betablockers for hypertension – when these have been discredited as routine therapy for this purpose for over a decade.

yet the Regulators led by the FDA – which is massively funded solely by Big Pharma as their ally- insists that vitamins, minerals and other long-proven natural supplement therapeutics, prime human hormones like melatonin and physiological human sexhormone creams , have to undergo $multimillion trials before they can be marketed as already long-evident safe effective therapies.

none of the vit D trials used the dose of vit D3 now recommended on solid evidence that we should all take – 80 (to 100)iu/kg/day or 2400-3000iu/kg/month of vitamin D3- ie about 150 000 – 200 000 iu to start and then per month for average adults – to maintain healthy 25OH vit D levels around 60-100ng/m (here our bloodlevels are usually between 10 and 20 ! because we take little dairy products, nuts and sunshine- we cover up and live indoors.) .

Most of the reported trials used only about 5% of the recommended vit D dose ie ~200 to 400iu/day ie 6 iu/kg/day! this dose does nothing except partly prevent rickets- in infants! Pregnant women are still routinely given such weak near-nonsensical doses of vit D.

and as Cannell’s review of the Autier analysis points out, the vitamin D trials trials under way – * in USA-Boston VITAL study 20 000pts) , Finland (FIND 18000 pts and UK(VIDAL1600pts ) , in some 40 000 subjects, due for publication only between 2017-2020- are using only 1600 to 3200iu vit D a day or about 48 000 to 96000iu/month ie perhaps 32iu (25 to 40) /kg/day. So they are testing still modest doses and blood level targets. .

ideally you should check your 25OH vit D and calcium levels to make sure you are on the right dose- but always taking some magnesia supplement, and at least 2 liter of water/ sodawater/clear fluid a day to avoid dehydration, kidney stones and vascular disease (which highdose calcium supplement eg 1000mg & vit D3 400iu/day cause).

8 April 2013 UPDATE: VITAMIN D3 THE AMAZING SUPPLEMENT

It is sad to record that Dr Walter Stumpf died suddenly a few months ago during ongoing correspondence. The world has lost a teacher of the century in both biological sciences and the humanities, metaphysics and philosophy,..

This week – as flu mushrooms in the southern hemisphere autumn- the Canadian Medical Association Journal April 3-8 features early-release articles on concerns about the Asian flu viruses and especially the SARS-nCorVirus. Is mass vaccination the answer? or did this in fact worsen mortality in previous North American epidemics of eg H1N1? which brings us back to global protection against infections and all major diseases with lowcost safe VitaminD3 at say 50 000iu(~700iu/kg)/week plus the other all-system protective supplements – eg multivitamins (especially vit C and K) and minerals especially magnesium, zinc, idine and selenium; and during epidemic times, major daily boost in vits D3 and C.

In December 2012 the University of San Diego published a useful researched update on vitamin D3 and breast cancer; pointing out again that while the increase in benefit obviously drops off with increasing dose, safe dose is up to at least 10 000iu a day or 70 000iu a week, to a bloodlevel around 100ng/ml; and toxic dose requires at least 40 000 iu a day chronically (if not 600 000iu/d as other evidence suggests). The projections for breast cancer reduction fit with the same team’s predictions in 2007.

So apart from maintaining good water intake, and avoiding taking ill-advised unbalanced solo calcium supplement, for optimal dosing in those with cancer or any other high risk, blood levels of both 25hydroxy vit D3, 1,25 calciferol, calcium, phosphate and creatinine, should be monitored occasionally, to avoid the rare risk of kidney stones and arterial/breast calcinosis.

Remember that magnesia, phosphate and vitamin C and K2 supplements are amongst the most important of at least 40 to accompany vitamin D3.

Last month three new studies affirmed the importance of vigorous vitamin D3 levels for genetic, heart and all health.

Holick’s group at Boston University show the profound .Influence of vitamin d status and vitamin d3 supplementation on genome wide expression of white blood cells. No studies have reported on how vitamin D status and vitamin D3 supplementation affects broad gene expression in humans. A randomized, double-blind, single center pilot trial was conducted for comparing vitamin D supplementation with either 400 IUs (n = 3) or 2000 IUs (n = 5) vitamin D3 daily for 2 months on broad gene expression in the white blood cells collected from 8 healthy adults. in the winter. CONCLUSION SIGNIFICANCE: Our data suggest that any improvement in vitamin D status will significantly affect expression of genes that have a wide variety of biologic functions of more than 160 pathways linked to cancer, autoimmune disorders and cardiovascular disease with have been associated with vitamin D deficiency. This study reveals for the first time molecular finger prints that help explain the nonskeletal health benefits of vitamin D

The magnitude of vitamin D inputs in individuals not taking supplements is unknown.. they reanalyzed 3000 subjects’ individual 25(OH)D concentration data from 8 studies involving vitD3 supplement. The total basal input (food plus solar) was calculated to range from a low of 778 iu/d in patients with end-stage renal disease to a high of 2667 iu/d in healthy Caucasian adults. Consistent with expectations, obese individuals had lower baseline, unsupplemented 25(OH)D concentrations and a smaller response to supplements. Similarly, African Americans had both lower baseline concentrations and lower calculated basal, all-source inputs. Seasonal oscillation in 4 studies ranged from 5.20 to 11.4 nmol/L, reflecting a mean cutaneous synthesis of cholecalciferol ranging from 209 to 651 iu/d at the summer peak. We conclude that: 1) all-source, basal vitamin D inputs are approximately an order of magnitude higher than can be explained by traditional food sources; 2) cutaneous, solar input in these cohorts accounts for only 10-25% of unsupplemented input at the summer peak; and 3) the remainder must come from undocumented food sources, possibly in part as preformed 25(OH).

August 2009 SUMMARY: Evidence is overwhelming that the prime sun-induced steroid hormone Vitamin D3 cholecalciferol – soltriol- is invaluable in 20fold higher dose ie perhaps 5000 to 10 000iu/day rather than has been preached to date (200- 400iu/d), as part of lifelong hormone replacement HRT to prevent all major chronic degenerative diseases in all humans living and working indoors. Effective dose of vitamin D3 supplement can reduce deathrate and disease by an astonishing 20%- that is indeed a panacea almost as good as other natural micronutrient supplements eg fish oil, metformin, and appropriate sex hormone replacement SHRT. It is becoming clear that with rare exceptions everyone- especially those with serious disease eg cancer, heart, lung, brain, nerve/muscle/bone/joint or inflammatory bowel diseases or chronic infections like TB HIV influenza or human papilloma virus – should take a daily supplement of about 10 000iu (1/4 mg) vitamin D for as little as ~ R10 US$1 a month ; ideally under supervision of some health professional. All that is required is occasional check of blood chemistry, and good diet and fluid intake.

And obviously because of vitamin D3’s benefits in lowering all diseases, when using vigorous dose vitamin D, one must expect to need to lower prescription drug treatments for diabetes, hypertension, depression, heart disease, lung disease, arthritis, infections etc as these ailments improve from the vitamin D replacement over months.

This review is especially appropriate on our Womens’ Day 9 August 2009 for a natural product so important for the health of women , that commemorates the year 1956 when 20 000 women marched in defiance of male despots’ fascist apartheid pass laws. The ages-old discrimination against women is epitomized by the pragmatic liberal economist Professor Ken Galbraith’s lecture to the Royal Society of Medicine in 1973 on the problem of unequal development and centralization of power in male technostructure – profit maximization.

No-where in business is this better shown than in Big Business creating demand by saturation marketing, including the medicalization of health. This involves disease-mongering through creating unnecessary concerns so as to expand markets among the well for patents eg blanket cholesterol or mammography or colonoscopy screening, or remedies for eg female arousal disorder, anxiety, reactive depression, mild-to-moderate hypercholesterolemia – when very few have been proven to need or benefit from such labels, procedures and drugs.

VITAMIN D3 SOLTRIOL : INFORMATION EXPLOSION:

The first of 46200 entries on Medline on vitamin D is from Oxford by Heaton 1922 . There are 272 500 entries on vitamins since 1918, the first specific one by Jack Drummond in 192o, but of course vitamin D was first identified by Mellanby 1919, preceded by vits A, B1 and C between 1909 and 1912. From a recent historical review (table 1) of hormones, vitamin D3 was perhaps the 7th hormone recognized after testosterone and estrogen (China 2600 years ago) , thyroid (1891) epinephrine secretin parathyroid and antidiuretic hormone.

Soltriolis an exquisite description for a sun-activated steroid, the cardinal prohormone vitamin D3 made from cholesterol via sunlight exposure. Soltriol is not in a 1964 Oxford Dictionary, nor is it’s etymology detectable on Google search; it was indeed invented by the pioneer polymath neurologist Dr Walter Stumpf . On Medline search for soltriol, the first result is Corradino 1973…

It is intriguing to read that Dr Stumpf graduated in medicine in 1952- and 50 years later in 2005 he wrote on his website: “From the microautoradiographic target recognition and related actions it follows that vitamin D has healing potential for prevention and treatment of various deficiencies and ailments, including old age: a PANACEA? If there is any compound that deserves being designated a panacea, the multifunctional heliogenic vitamin D appears a suitable candidate. Philosophical consideration: “Vitamin D”, the term does not reflect its significance. I have used instead SOLTRIOL in several publications as a more appropriate designation. – Is there not a link to Heraclitus emanation of “ ever-living fire ”? The cosmic solar fire (Soltriol) as the sustaining life force, providing wave length energies for Temperature, Visible Light , and Ultraviolet B “. ” The Main Biological Role of Vitamin D is Seasonal Adjustment of Vital Functions: These include regulation of growth, reproduction, survival stress response; endocrine and exocrine secretion, cell proliferation, cognition and mood; neuro-motor, neuro-endocrine, and neuro-sensory functions, immune response, cardio-vascular and gastro-intestinal functions, regulation of calcium and other mineral levels, cell proliferation and protein synthesis-differentiation.

Considering the decades of vitamin D use for its other benefits, it is ironic that a 1999 University California website on The History of Vitamin D has never been updated to cover more than the anti-rickets protection from vitamin D. But as Prof Stumpf writes to me today, ultimately it is the sun that is the panacea, transmitting it’s healing powers via the skin-activated messenger hormone vitamin D.

It is now almost a year since this column last reviewed vitamin D3’s benefits against all major diseases (see table) – during which year scores of new randomized controlled trials RCTs of vitamin D have appeared- there are now some 1680 RCTs on it since 1965. Carpenter 1999 reviews Forgotten Mysteries in the History of Vitamin D.

Women have a raw deal: due to their prime role and innate sense for survival of the species, for nuturing and caring, they live about 10% longer than their mates, but as a result endure far more illness, as well as assault, disability and murder (mostly inflicted by the careless male).

PROTEAN STEROIDS, PROTEAN FUNCTIONS: Calcitriol is one of many human steroids that include the sex hormones, aldosterne and digoxin; as well as nonhuman steroids which also have important medicinal use- like phytosteroids, equine steroids like the equilins eg premarin, and the important ecdysteroids in insects and some plants. Stumpf has again stressed the wide distribution in humans of vitamin D receptors VDRs, indicating their importance in protean human functions far beyond calcium regulation.

VITAMIN D AND ALL-CAUSE MORTALITY:it is just a year since Melamed ea from USA showed that having low vitamin D (as opposed to high level) increases all-cause mortality by 26%- thus taking submaximum safe dose of vitamin D can improve chance of survival by about 20%. This for as little as R10/month – $1- in South Africa.

In 2000, the Seven Country Study Group showed that ” saturated fat,vitamin C and smoking are the major determinants of all-causemortality at the population level” ie the higher the fat and smoking intake and the lower the vitamin C, the higher the deathrate. We now know better- serious vitamin D deficiency joins the list, which of course includes alcoholism. .

VITAMIN D AND CARDIOVASCULAR DISEASE CVD

Pizzorno 2009 reviews the strong evidence of the importance of balanced vitamins A D and K supplements in reversing the epidemics of both CVD and osteoporosis.

VITAMIN D AND DEPRESSIVE/NEURODEGENERATIVE DISEASE

over 20 articles already this year attest to the importance of vigorous vitamin D levels in reducing these diseases.

The much higher incidence of autoimmune diseases in women – especially SLE systemic lupus erythematosis and RA rheumatoid arthritis- let alone far higher younger female risk for fractures- must have been obvious for millennia. So obviously genetic female factors play a major role in these diseases – now surely attributable largely to the reproductively necessary absence of the Y chromosome, and thus the 100fold lower testosterone: estradiol T:E2 ratio in women (perhaps 2:1) than in men (in youth, >200:1).. It is common cause that estrogen is immunostimulant whereas testosterone and progesterone (like vitamin D) are immunomodulating. Hence testosterone and progesterone levels soar during pregnancy to prevent the mother rejecting her foetus. This partly also explains why vigorous vitamin D supplement also greatly improves fertility and pregnancy outcome.

VITAMIN D AND RHEUMATOID ARTHRITIS: many studies show the benefits of the prime anabolic steroids- vitamin D and androgen (Devis 1950) supplements- in treatment of all inflammatory disease, especially when inflammation itself weakens bone and all other tissues. The latest – last month (Chabchoub 2009)- shows “a possible role for XCI mosaicism in the pathogenesis of RA and thyroid disease and may in part explain the female preponderance of these diseases”. But the first and only randomized controlled trial of the effect of vitamin D on modifying RA appears in 1973 (Brohult) and the only open trial (Andjelkovic 1999) in RA showed that “alphacalcidiol is a powerful immunomodulatory agent with fairly low hypercalcemic activity”.

VITAMIN D INTOXICATION: The low toxicity of vitamin D3 is fortunate because while it is ideal to monitor vitamin D levels on effective replacement, the blood test costs about R660- $80- locally; hence all one needs to do is exclude kidney problems (which may need even higher dose of vitamin D3), and risk of kidney stones- but perhaps checking blood calcium and creatinine at baseline and occasionally, and ensuring balanced supplement of calcium-magnesium – boron-zinc-manganese-(iron if deficient) and vitamins B, C, D and K. Since vitamin D intoxication (toxic rise in blood calcium- hypercalcemia) in some opinions requires ~>600 000iu/day for months, ths is inconceivable unless one were to swallow say twelve 50 000iu vitamin D every day for months. So the only recognized form of vitamin D intoxication could be an industrial accident involving mistaken use of vitamin D concentrate in medicine.

HYPERCALCEMIA HIGH BLOOD CALCIUM: medical causes are rare without gross calcium overdose (milk alkali syndrome) or other specific symptomatic diseases – eg primary hyperparathyroidism, sarcoidosis, tuberculosis, and lymphoma.And fortunately most patients with these diseases and hypercalcemia are far more likely to benefit from therapeutic treatment with vitamin D than worsen on it.

OVERDOSE: HYPERVITAMINOSIS D: WIKI says “Vitamin D stored in the human body as calcidiol (25-hydroxy-vitamin D) has a half-life of about 20 to 29 days.[17] Ordinarily, the synthesis of bioactive vitamin D hormone is tightly regulated, and prevalent thinking is that vitamin D toxicity usually occurs only if excessive doses (prescription forms or rodenticide[38] . Serum levels of calcidiol (25-hydroxy-vitamin D) are typically used to diagnose vitamin D overdose. In healthy individuals, calcidiol levels are normally between 32 to 70 ng/mL (80 to 175 nmol/L), but these levels may be as much as 15-fold greater in cases of vitamin D toxicity. Serum levels of bioactive vitamin D hormone (1,25(OH2)D) are usually normal in cases of vitamin D overdose. Symptoms include Dehydration Vomiting Decreased appetite (anorexia) Irritability Constipation Fatigue.

Overdose of vit D3 has been observed at 1925 µg/d (77,000 IU per day). Acute overdose requires between 600,000 and 1,680,000 IU per day over a period of several days to months, with a safe intake level being 10,000 IU per day.

A 2007 risk assessment suggested that 250 micrograms/day (10,000 IU) in healthy adults should be adopted as the tolerable upper limit.[39]In adults, sustained intake of 100,000 IU can produce toxicity within a few months.[2]For infants (birth to 12 months) the tolerable UL is set at 1000 IU, and 40,000 IU has been shown to produce toxicity within 1 to 4 months. All known cases of vitamin D toxicity with hypercalcemia have involved intake of or over 40,000 IU)[42].

Although normal food and pill vitamin D concentration levels are far too low to be toxic in adults, people taking multiples of the normal dose of codliver oil may reach toxic levels of vitamin A, not vitamin D, [43] if taken in an attempt to increase the levels of vitamin D. Most officially-recorded historical cases of vitamin D overdose have occurred due to manufacturing and industrial accidents.[42]

Some symptoms of vitamin D toxicity are a result of hypercalcemia caused by increased intestinal calcium absorption. Vitamin D toxicity is known to be a cause of high blood pressure.[45] Gastrointestinal symptoms of vitamin D toxicity can include anorexia, nausea, and vomiting. These symptoms are often followed by polyuria (excessive production of urine), polydipsia (increased thirst), weakness, nervousness, pruritus (itch), and eventually renal failure. Other signals of kidney disease including elevated protein levels in the urine, urinary casts, and a build up of wastes in the blood stream can also develop.[2] In one study, hypercalciuria and bone loss occurred in four patients with documented vitamin D toxicity.[46] Another study showed elevated risk of ischaemic heart disease when 25D was above 89 ng/mL.[47] Vitamin D toxicity is treated by discontinuing vitamin D supplementation, and restricting calcium intake. If the toxicity is severe blood calcium levels can be further reduced with corticosteroids or bisphosphonates. In some cases kidney damage may be irreversible.[2]

Exposure to sunlight for extended periods of time does not normally cause vitamin D toxicity.[42] This is because within about 20 minutes of ultraviolet exposure in light skinned individuals (3–6 times longer for pigmented skin) the concentration of vitamin D precursors produced in the skin reach an equilibrium, and any further vitamin D that is produced is degraded.[48]Maximum endogenous production with full body exposure to sunlight is 250 µg (10,000 IU) per day.[42]”

VITAMIN D AND SEX:

Biologically, the most imperative function for species survival is sex- reproduction. Vitamin D is clearly a potent anabolic reproductive steroid like testosterone: The first paper on this association on Pubmed appears in 1963 from Russia (Gokinaeva).

Mirzahossein in 1996 showed that,” given in the critical period of foetal imprinting, vitamin D may influence steroid hormone-receptor commanded events for life in a way similar to synthetic steroid hormone analogues”. So as with marine omega3., it is crucial that future parents take enough vitamin D.

Friedrich 2002 showed that even prostate, colon and normal cervical tissue and cervical cancer cells have VDRs – vit D receptors- and may be new targets for cancer prevention or cancer treatment.

VITAMIN D AND SLE- SYSTEMIC LUPUS ERYTHEMATOSIS: on medline the first reference to immunosuppression with vitamin D was by Bourdial 1963 on nasal allergy, and the first for vitamin D and immunomodulation is by Nagler & Pollack 1986.:

However, the first paper on the importance of Vitamin D3 deficiency in SLE appeared in Germany 1963, but the first paper in English and from an English country only in 1979 (O’Regan).

The focus throughout has been on the benefit of vitamin D in reversing the hyperimmunity of SLE, but of course vitamin D is equally important in preventing both the osteoporosis of inflammation, the fracture and wasting risks of cortisone treatment, and the vascular disease associated with SLE. In the last year alone there have been 10 such SLE – vitamin D major studies – 7 from the Americas and 3 from Europe.

SLE as well as plain lupus of the skin are generally regarded as disease that requires protection from the sun.

Now this week Wright 2009 shows that in children, SLE is associated with vitamin D deficiency, particularly among those subjects with SLE who are overweight.

VITAMIN D, SUNLIGHT, SLE AND CANCER:

The first case of SLE associated with cancer ( meningioma and cervix)- is reported by Williams 1956. The latest – last month- highlights increased risk of lymphoma, cervix and bronchus cancers.

Search for malignant melanoma MM and SLE finds the first reference in 1963. yet most of the papers are about reactions to interferon therapy, or immune markers- there is one solitary case report (1991 Sulkes, Israel) of a patient with indolent SLE who after 15 years developed and died of rapidly spread of MM. These authors comment on the infrequent association of SLE & solid cancers, the commonest being uterus and bladder.

So it is exciting that while more sun exposure causes skin cancer and especially cutaneous melanoma CMM, (Tuohimaa 2007), sun exposure also improves survival from CMM- and from a wide range of internal cancers – (especially stomach, colorectal, liver and gallbladder, pancreas, lung, female breast, prostate, bladder and kidney cancers). This favourable effect of more sunshine is obvious when comparing the lower cancer and heart disease deathrates in sunnier southern versus the darker northern countries. Only rare skin diseases eg porphyria cutanea tarda are contraindications to sun exposure of the skin. But at least one study Holme 2008 shows vitamin D deficiency in erythropoetic porphyria.

Professor Halstead 2008 (and many others) conclude that the high fructose corn syrup routinely used in fast foods and cooldrinks in first-world manufacturing is rapidly increasing obesity, lipidemia (and metabolic syndrome and cancer); while folic acid food fortification is causing low B12 levels and thus possibly increasing dementia, vascular disease and advanced precancerous colorectal adenomas and breast cancer. This trend is aggravated by at least three scientifically unvalidated obsessions of Regulators and the Medical hierarchy:

1. low diet cholesterol in those with mild to moderate cholesterolemia;

Protection from both cancers and SLE is probably associated with higher vitamin D level above ~100nmol/L. Both lupus and cancers are due to altered immunity. But SLE is due to increased autoimmunity- hence cancers are infrequent during active SLE; whereas cancers are due to reduced immunity – hence are associated with immune suppression, whether by cortisone (including stress) / chemotherapy, or deficiency of vitamin D – dietary and lack of sunshine..

While there is no clear overall relationship of statins to osteoporosis or cancer, Kunitomo 1989showed that cholesterol reduces and corticosteroids enhance the toxicity of vitamin D in rats. Montagnani 1994 showed that pravastain does not interfere with the circulating levels of the main vitamin D metabolites.

VITAMIN D AND INFECTION:

For an acute infection, Cannell and Hollis 2008 suggest vitamin D in an antimicrobial dose of 2000iu/kg eg 120 000 iu a day for 3 days- to produce enough of the naturally occuring antibiotic cathilicidin. Ginde 2009 show that those with high vitamin D levels have less respiratory infections. This column has previously reviewed the dramatic benefits of vitamin D on infection mortality in AIDs- TB patients. Obviously one is going to be cautious pushing vitamin D in a patient with known kidney stones, or hypercalcemia.

VITAMIN D : WHY THE INCREASING DEFICIENCY, NEED FOR SUPPLEMENT ?

Never mind the poor and chronically ill, the aging especially need much more vitamin D, and benefit the most. Even in a sunny fishing nation like Spain, elderly women do not get enough vitamin D from fish or other foods, and most have suboptimal blood levels of it.

Apart from dietary intolerance and obsession reducing intake of cholesterol and dairy products, the vitamins and minerals in particular have been greatly depleted and imbalanced in commercially produced- and especially genetically-modified food. And while increasing longevity, food scarcity -poverty and mushrooming prices (cartel pricefixing that is ignored by well-paid politicians and regulators) – are prime causes, Politicians and Regulators have worsened this by falling decades behind in ignoring the leading 20th pioneer nutritionist/ economists like the USA’s Professors Linus Pauling the unique double Nobel prizewinner prophet of vitamin C and peace; Ken Galbraith; and the UK’s SirJack Drummond. The latter two respectively brought the Allies (under FD Rooseveld and WS Churchill) through WW2 by putting farming- healthy food production and pricing- as the painfully obvious priority- which selfserving gluttonous politicians like Nixon, Bush, Kissinger, Mugabe and Mbeki, and most others leaders (who support, not just tolerate such despots) simply ignore since they detest “surplus people”- the honest poor; if not also hardworking farmers.

It is no coincidence that Pauling and Galbraith both graduated from agricultural colleges. And no coincidence that all three nutritionists were the targets of politician-business moguls because of the obstacles they posed to the profiteering national economic sabotage that is the lifeblood of ruthless businessmen-capitalists from before Nixon- Connolly- Reagan- Kissinger and Thatcher, through to the Bushes and Blair and Montsano-GD Searle, Mbeki and Zuma, and the arms, oil, banking, mining, media, food, sex, tobacco-alcohol and medical-big pharma industry mafiosi cartel who make or break presidents and governments.

James Ferguson makes a strong case for The Vitamin Murders, that Drummond (and his family) were butchered in a Vitamin Industry contract in France as a lesson to do-gooders because his advocacy of the primary role of good natural nutrition and vitamins was such an obstacle to the fast food and synthetic drug industry. Conspiracy theorists could argue that, like Pauling’s vitamin C, the Drug Industry have through the FDA managed to ensure that only this year is the FDA grudgingly moving to raise the Recommended daily Allowances of vitamin D (and C) even fractionally above the present rickets- (and scurvy) preventing doses, as opposed to their modest 25 to 50fold fold higher intakes that have been known already for decades to be both safe and major benefit against all diseases.

John Le Carre’s The Constant Gardner echoes that ongoing conspiracy scenario, the battle between Big Pharma with it’s drug lobbyists (including the USA FDA and the European Union’s European Medicine’s Authority, and leading politicians) to promote their lucrative modern synthetic chronic drugs (none of which have been shown to reduce all-cause disease and mortality as do natural supplements), versus nutritionists and informed consumers who know that broad natural supplements (vigorous vitamins, minerals and biologicals) to bolster the failing adulterated food chain are more important and effective than any patented designer drugs in combating all disease. Unfortunately the necessary advocacy for natural supplements has been muddied by fraudsters like the Big Pharma- FDA- academia cartel (who swamp the medical literature with trial and review papers favouring their snake oils), the Rath Foundation, and our local dissidents against reason like Mbeki, and Drs Manto Tshabalala-Msimang, Nkosasama Zuma and Olive Shishana.

CONCLUSION: In 2006 Dr Walter Stumpf in THE DOSE MAKES THE MEDICINE wrote: “in recent years, discussion raged about the negative effects of estrogen-replacement therapy and its relationship to cancer. In numerous articles, the side-effects of estrogen treatment were highlighted in a generalized fashion and, although consideration was given to the duration of treatment, the relationships to dose (let alone type and route of estrogen) were frequently left out. And yet, considerations of dose and time in pharmacology and toxicology are paramount.
Similarly, awareness of proper dosage is crucial to the development of future vitamin D therapies. Physiologic dosing of vitamin D does not cause hypercalcemia – hypercalcemia is related to overdosing ie closer to 100 000iu/day. Considering the many target tissues that are unrelated to systemic calcium regulation, most therapeutic effects of vitamin D occur independently of the high-dose systemic calcium effects. Because of the biased focus on calcium, the many other effects tend to remain unnoticed and hidden. Future research needs to give more consideration to dose-effect relationships by monitoring target functions independently of systemic calcium regulation.
New therapeutic applications of vitamin D can be established for cardiovascular, neurological, endocrine, immune, gastrointestinal, reproductive and other diseases, including posttraumatic and gerontological deficiencies, in which the polyfunctional effects of the hormone not only come to bear, but can also be controlled and maximized for optimal health.”

Since the global population shift from rural to city life and work the past century ie in our lifetispan, humans have largely gone from being healthy longlived outdoor food-producing workers living on their own fresh produce including organically grown unadulterated fresh food and dairy products – or fish- (rich in micronutrients), to working mostly indoors and consuming largely micronutrient-depleted food as well as multiple noxious deliberate industrial pollutants- from sugar and alcohol to estrogenics, pesticides, heavy metals, cornsyrup and aspartamate.

Like fish oil is the most important food extract we have (and businessmen are ruthlessly harvesting to extinction), vitamin D3 has become the anti-disease vitamin of the past decade, joining vitamins C & B as the panacea vitamins that can and should be supplemented in far higher dose than anti-vitamin “Regulators” and professional researchers and associations (with vested interests in protecting their funder- Big Pharma) approve.

But as the more affluent age and increase in numbers, the micronutrients that deplete (with longevity, the deteriorating food chain, and unnecessary drugs),- especially vitamins K, chondroglucosamine, N-acetyl cysteine, alphalipoic acid, Co-Q10, arginine, carnitine, carnosine, riboseand the marine EPA and DHA- are fast becoming the “vitamins” of the next decade.

Tragically, edible marine products especially marine omega3 EPA+DHA are rapidly becoming so scarce that the vast majority of people can neither source nor afford the minimum optimal gram a day, until science breaks through to synthesize these uniquely beneficial free fatty acids. But at least the supply of minerals, and vitamins including D3, is inexhaustible and therefore freely available at reasonable cost.

ndb

dedicated to Dr Walter Stumpf, whose >300 papers (~24% on vitamin D) on Medline apparently span 1963 to 2008- on vitamin D the first in 1979, the last 30years later appropriately on Vitamin D and the digestive system. By comparison, Pubmed lists only 3 papers by Albright, in 1938-9.

update: 16 Dec 2014 THE RISKS OF MODERN ANTIHYPERTENSIVE DRUGS: Pubmed search for ANTIHYPERTENSIVE DERMATITIS REACTIONS brings up >156 papers from 1970 (on practolol, propranolol, atenolol, labetolol, hydralazine, ACEI); we first encountered practolol (BBlocker) problems in the ’70s; and captopril (ACEI) dermatitis about 1980; Dermatitis has also been reported since 1987 with calcium channel blockers. WHY USE ACEI/ARBS and BETABLOCKERS -with their added airways and circulatory risks -EXCEPT AS LAST RESORT? when these are now routinely combined with other synthetic designer drugs clopidogrel (a sulfonamide) , or /and non-sulfonamide warfarin, aspirin, other NSAIDs and statins; sulphonylureas, glitazones, which cause serious multiple complications including dermatitis.

Refs: 1. Immunopharmacol Immunotoxicol. 2013 :35:447-50 “Cutaneous antihypertensiveadverse drug reactions (ADRs) have been frequently reported. Vena, De Simone ea University of Bari, Italy reported Eczematous reactions due to angiotensin-converting enzyme inhibitors ACEIs or angiotensin II receptor blockers ARBs in 23 hypertensive patients patients aged 66-87 years; 19 of them were taking another drug in addition to the suspected antihypertensive medication and 15 were on polytherapy with three or more drugs to treat multiple comorbidities. The antihypertensive culprit agents were (ACE) inhibitors in 9 patients, ACEI combined to hydrochlorothiazide (HCT) in 7 subjects, ARBs alone in 2 patients and associated with HCT in 5 cases. Eczema was generalized in 16 patients and localized in 7 cases, with predominant involvement of lower limbs. Such lesions developed after a latency of 4-30 months and were associated with moderate-to-severe itch, usually unresponsive to oral antihistamines. Histopathology was spongiotic dermatitis with possible associated psoriasiform skin changes.”

13 December 2014: latest analyses of all antihypertensive trials confirm that LOWDOSE (potassium-sparing) diuretic- eg amilozide- LOWDOSE reserpine, and if needed as 4th drug, calcium channel blocker eg amlodipine, each individually lower all major events including MORTALITY, ( and refractory lowers refractory pain). Betablockers, ACEI and ARBs do not reduce mortality- and have major adverse effects. .

Thomopoulos ea (Univs Athens & Milan) J Hypertens Dec 2014Effects of various classes of antihypertensive drugs on outcome incidence in hypertension,asks which BP-lowering drug classes are effective in reducing MORTALITY? In 55 RCTs (~200 000 individuals) all common antihypertensive drugs lowered BP , stroke, and major cardiovascular events; but in 2014 use, only a diuretic (even lowdose); and calcium antagonists gave significant reductions of all outcomes including mortality.

PAIN SUPPRESSED BY RESERPINE:S Afr Med J.1991;80:176-8. Significant cost-saving with modification of antihypertensive therapy. Keeton & Monteagudo, Univ.Cape Town. 30 patients on nifedipine for hypertension or chest pain were followed up for 6 months after alternative therapy- Reserpine combined with a thiazide- was instituted: blood pressure control improved and no serious side-effects were encountered. This reduced the monthly cost by 73%. Although a self-assessment depression inventory was completed by 21 patients, our study does not fully evaluate the impact on quality of life. The likelihood of side-effects is small–provided the maximum daily dose of reserpine does not exceed 0.1 mg. A more considered approach is needed in the choice of antihypertensive agents.

The progression of essential HBP begins with prehypertension in persons aged 10-30 years (by increased cardiac output) and then advances to early HBP in persons aged 20-40 years (increased peripheral resistance ), then to established HBP in persons aged 30-50 years, and finally to complicated HBP in persons aged 40-60 years.

Hence to prevent HBP becoming established and complicated by midlife, both the lifestyle/ nutritional factors, and the neural- stress and the RAAS renal-aldosterone- angiotensin systems – need to be optimized in young adulthood, in the early workplace if not childhood ie at school: with reintroduction at school of compulsory physical education/sport; banning of tobacco, refined sugar and retail salt sale; universal ingestion 3 times a week at least of a tsp of codliver oil equivalent (before it becomes unobtainable;) and a tblsp of virgin coconut oil; and if bloodpressure does not normalize, addition of at least 3 times a week 1/2 reserpine ie 0,125mg and 1/2 amilozide ie 27.5mg , to address most of the risk factors, as detailed below a week ago. .

Kostis ea, UnivHarvard; Rutgers,. Columbia,Texas, Am J Cardiol.2014 Feb examined Competing cardiovascular and noncardiovascular risks and longevity in the Systolic Hypertension in the Elderly Program SHEP with chlorthalidone-based stepped care (n = 2,365) or placebo (n = 2,371) for 4.5 years,. all participants were advised to take active therapy thereafter. At the 22–year follow-up, gain in life expectancy free from CV death in the active treatment group was 145 days ( p = 0.012). The gain in overall life expectancy was smaller (105 days)because of a 40-day (95% CI -87 to 161) decrease in survival from non-CV death. Compared with an age- and gender-matched cohort, participants had markedly higher overall life expectancy ( p = 0.00001) and greater chance of reaching the ages of 80 (81.3% vs 57.6%), 85 (58.1% vs 37.4%), 90 (30.5% vs 22.0%), 95 (11.9% vs 8.8%), and 100 years (3.7% vs 2.8%). In conclusion, Systolic Hypertension in the Elderly Program participants had higher overall life expectancy than actuarial controls and those randomized to active therapy had longer life expectancy free from CV death but had a small increase in the competing risk of non-CV death

The2013 Statement by the International & American Societies of Hypertension( including all continents and South Africa) includes amiloride-HCTZide ; and reserpine 0.1 mg/day in the array of drugs to be combined for optimal BP control. “Thiazide-like Diuretics: reduction of major cardiovascular CVD and stroke events have been established. Main side effects are metabolic (hypokalemia, hyperglycemia, hyperuricemia), which can be reduced by using low doses (eg, 12.5 mg or 25 mg of HCTZ) or by combining these diuretics with potassium-sparing agents eg angiotensin-blockers, amiloride etc . Note: Thiazides plus b-blockers are also an effective combination for reducing blood pressure, BUT since both increase blood glucose concentrations, use with caution in patients at risk for diabetes. Angiotensin-converting enzyme inhibitor ACEIs’ main side effect is cough (most common in women and in patients of Asian and African background). Angioedema is an uncommon but potentially serious complication that can threaten airway function, and it occurs most frequently in black patients.

Given the above -quoted longstanding established dangers of bblockers and ACEI; and that the majority of older State chronic patients around Cape Town are black and Asian women, overweight hypertensive diabetic smokers, it is negligence on the part of State authorities that most State patients are treated with deleterious betablockers (atenolol), Angiotensin blockers and HCTZ ; instead of primarily with the longproven optimal lowdose reserpine, amilozide and amlodipine.

30 Nov 2014 NEW studies below confirm that the renin-angiotensin-aldosterone system RAAS and the autonomic nervous systems ANS are the two networksthat primarily regulate bloodpressure. In baseline treatment of common essential HBP, Increasing recent research points to the prime role of amiloride – thiazide combination eg Moduretic, Amiloretic – and arginine (nitric oxide stimulant) – addressing the RAAS; – withreserpine addressing the ANS and anxiety.

and the cardiorespiratory risks of betablockers, and ARBs. The evidence in fact supports use of amiloride lowdose preventatively in a highrisk prehypertensive population. just as the prohormone metformin is used preventatively in reversing weight gain to prevent diabetes, atheroma and PCOS inferti9lity..

refs: 1. Nutr Hosp. 2014 Dec.ALDOSTERONE: A CARDIOMETABOLIC RISK HORMONE? Pereira , Bressan ea.University of Viçosa, Brazil.. Aldosterone is a component of the renin-angiotensin-aldosterone system, classically known for its role in sodium and water retention. Besides its renal effects, aldosterone is associated with the pathogenesis and progression of metabolic syndrome components. Diet can affect plasma aldosterone levels; high fructose and fat intake can lead to increased aldosterone levels, whereas the effect of sodium intake remains controversial. Adipose tissue, particularly visceral tissue, appears to produce a lipid-soluble factor that increases aldosterone production. Patients with metabolic syndrome have higher aldosterone levels; moreover, an increased cardiometabolic risk associated with insulin resistance could be partially mediated by the action of aldosterone via mineralocorticoid receptors. Even a subtle activation of this hormonal system may have deleterious effects on the glucose and lipid metabolism related to metabolic syndrome.

2. Semin Nephrol Sept 2014 .. Pathophysiology and Treatment of Resistant Hypertension: The Role of Aldosterone and Amiloride-Sensitive Sodium Channels.Judd EK1, Calhoun DA2, Warnock DG2. University of Alabama. Resistant hypertension is a clinically distinct subgroup of hypertension defined by the failure to achieve blood pressure control on optimal dosing of at least 3 antihypertensive medications of different classes, including a diuretic. In the absence of demonstrable renal, vascular and common endocrine causes, pathophysiology of hypertension can be attributed to aldosterone excess in more than 20% of patients with resistant hypertension. Dogma attributes increase in blood pressure seen with increases in aldosterone to its antinatriuretic effects. However, emerging research, has identified and defines the function of amiloride-sensitive sodium channels eNaC and mineralocorticoid receptors in the systemic vasculature, challenges impaired natriuresis as the sole cause of aldosterone-mediated resistant hypertension. It thus highlights the cardinal role of amilozide in hypertension therapy.

3. Pflugers Arch. 2014 Nov: Salt controls endothelial and vascular phenotype.Kusche-Vihrog , Brand ea. University of Muenster, Germany. High salt (NaCl) intake promotes development of vascular diseases independent of rise in blood pressure, whereas reduction of salt consumption has beneficial effects for the arterial system. We focus on endothelial Na+ channel (EnNaC)-controlled nanomechanical properties, since high Na+ leads to an EnNaC-induced Na+-influx and subsequent stiffening of endothelial cells. Mechanical stiffness of the endothelial cell (i.e., the endothelial phenotype) plays a crucial role as it controls the production of the endothelium-derived vasodilator nitric oxide (NO) which directly affects the tone of the vascular smooth muscle cells. In contrast to soft endothelial cells, stiff endothelial cells release reduced amounts of NO, the hallmark of endothelial dysfunction. This endothelium-born process is followed by the development of arterial stiffness (i.e., the vascular phenotype), predicting the development of vascular end-organ damage such as myocardial infarction, stroke, and renal impairment. In this context, we outline the potential clinical implication of arginine, direct (amiloride) and indirect (spironolactone) EnNaC inhibition on vascular function.

4. J Clin Hypertens (Greenwich). 2014 Jan Epithelial sodium channel eNaC inhibition by amiloride on blood pressure and cardiovascular disease risk in young prehypertensives.Bhagatwala , Dong ea, Regents University, Augusta, GA.. Overactivity of epithelial sodium channel (ENaC) is considered to be one mechanism underlying obesity-related blood pressure (BP) elevation. In a nonplacebo-controlled clinical trial , the authors aimed to comprehensively evaluate the effects of amiloride monotherapy, an ENaC blocker, on BP and cardiovascular risk in young adults with prehypertension (n=17). Following 10 mg daily amiloride for 4 weeks, peripheral systolic BP (SBP), central SBP, and carotid-radial pulse wave velocity were significantly reduced by -7.06±2.25 mm Hg, -7.68±2.56 mm Hg, and -0.72±0.33 m/s, respectively, whereas flow-mediated dilation was significantly increased by 2.2±0.9%. Following amiloride monotherapy for 4 weeks, a significant increase in serum aldosterone was observed (5.85±2.45 ng/dL). ENaC inhibition by amiloride may be used as an early intervention to halt the progression to full hypertension and cardiovascular disease in young adults with prehypertension.

6. Hypertension. 2012 .Double-blind, placebo-controlled, crossover trial comparing the effects of amiloride and hydrochlorothiazide on glucose tolerance in patients with essential hypertension. Stears, Brown ea University of Cambridge. Hypertension guidelines advise limiting dose of thiazide diuretics and avoiding combination with β-blockade, because of increased risk of diabetes mellitus. We tested whether changes in the 2-hour oral glucose tolerance test could be detected after 4 weeks of treatment with a thiazide and could be avoided by switching to amiloride. . For similar blood pressure reductions, there were opposite changes in glucose between the 2 diuretics (P<0.0001). There was a negative correlation between Δpotassium and Δ2-hour glucose (r=-0.28; P<0.0001). In 2 crossover studies, 4 weeks of treatment with a thiazide diuretic impaired glucose tolerance. No impairment was seen with K(+)-sparing diuretic or β(1)-selective blockade. Substitution or addition of amiloride may be the solution to preventing thiazide-induced diabetes mellitus.

7. Am J Physiol Endocrinol Metab. 2008 Dimethyl amiloride improves glucose homeostasis in mouse models of type 2 diabetes.Gunawardana , Piston ea .Vanderbilt University, Nashville, TN. Dimethyl amiloride (DMA) enhances insulin secretion in the pancreatic beta-cell. DMA also enhances time-dependent potentiation (TDP) and enables TDP to occur in situations where it is normally absent. As we have demonstrated before, these effects are mediated in part through inhibition of neuronal nitric oxide synthase (nNOS), resulting in increased availability of arginine. Thus both DMA and arginine have the potential to correct the secretory defect in diabetes by enabling or enhancing TDP. In the current study we demonstrated the ability of these agents to improve blood glucose homeostasis in three mouse models of type 2 diabetes. The pattern of TDP under different conditions indicates that inhibition of NOS is not the only mechanism through which DMA exerts its positive effects. Thus we also have explored another possible mechanism through which DMA enables/enhances TDP, via the activation of mitochondrial alpha-ketoglutarate dehydrogenase.

27 Nov 2014THE IMPORTANCE OF NORMALIZING RESISTANT HYPERTENSION : THE ALLHAT TRIAL Furberg ea December 2002 was the biggest trial that compared a thiazide with other standard antihypertensive drugs in highrisk patients, and confirmed thiazide’s superiority over amlodipine, lisinopril, and especially doxazosin. This was confirmed in the smaller shorter CONVINCE multinational trial Black ea a few months later, which showed that as single therapy, verapamil was inferior to a thiazide or atenolol.

24 Nov 2014NOTE how Big Pharma has lied in corrupting theWikipedia section (in italics below) onreserpine so as to try to further sideline this excellent natural drug: the adverse highlights below in red are based on ancient data from when Reserpine was used decades ago in the West in 5 to 50 times higher doses than have been used without adverse effects in trials the past 20 years, and for centuries in India as the parent Rauwolfia:

Reserpine: “because of the development of better drugs for these purposes and because of its numerous side-effects, it is rarely used today.Nonsense. This ignores the numerous side-effects of betablockers, ACEI, ARBs and CCBs other than amlodipine. The reserpine-induced depression is considered by some researchers to be a myth, while others claim that teas made out of the plant roots containing ie lowdose reserpine has a calming, sedative action that can actually be considered antidepressant.[4] Notably, reserpine was the first compound shown to be an effective antidepressant in a randomized placebo-controlled trial.[5] It may take the body days to weeks to replenish the depleted VMAT, so reserpine’s effects are long-lasting- a major advantage if patients take drugs irregularly. Tryptophan is the starting material in the biosynthetic pathway of reserpine, and is converted to tryptamine by tryptophan decarboxylase enzyme. Various enzymatic conversion reactions lead to the synthesis of reserpine from strictosidine.[8]

“This depletion of dopamine can lead with reserpine overdose to drug-induced parkinsonism. THIS IS ONLY IN EXCESSIVE RESERPINE DOSE. Reserpine has been discontinued in the UK for some years due to its numerous interactions and side effects. nonsense– it was discontinued to protect Big Pharma newer antihypertensive drugs eg Cardura, metoprolol, lisinopril; ARBs, Exforge etc .

“THE Reserpine-THIAZIDE COMBINATION (WITH OR WITHOUT OTHER OLD DRUGS EG POTASSIUM-SPARERS AND HYDRALAZINE) is one of the few antihypertensive medications that have been shown in randomized controlled trials to reduce mortality:

“Reserpine is rarely used in the management of hypertension today.NONSENSE – that is merely the explicit wish and intent of Big Pharma. Reserpine is listed as an option by the JNC 7.[17] Reserpine is a second-line adjunct agent for patients who are uncontrolled on a diuretic when cost is an issue.[18] The daily dose of reserpine in antihypertensive treatment is as low as 0.1 to 0.25 mg – IN FACT 0.0625 t0 0,125MG/d. At doses of less than 0.2 mg/day, reserpine has few side effects, the most common of which is nasal congestion- SO WE NEVER PERSIST WITH above 0.125mg/d

Nine years ago we reviewed in the BMJ why reserpine plus thiazide is The best-proven two-drug hypertension regime in primary care,

update 20 Nov 2014 the Sept 2014 influential French review Prescrire Intreviews the available evidenceTreating essential hypertension- As in 2004, the first choice is usually a thiazide diuretic TZD .. The current treatment threshold for hypertensive adults without diabetes or cardiovascular or renal disease is blood pressure above 160/90-100 mmHg. Apart from certain diuretic-based combinations, the use of combinations of antihypertensive drugs as first-line therapy has not been evaluated in terms of the complications of hypertension. systematic meta-analyses of tens of thousands of patients have compared the main classes of antihypertensive drugs against each other and against placebo. Compared with placebo, only low-dose TZDs and angiotensin-converting enzyme (ACEI) inhibitors have been shown to reduce all-cause mortality in hypertensive patients. They prevent about 2 to 3 deaths and 2 strokes per 100 patients treated for 4 to 5 years. Systematic reviews conclude that neither calcium-channel blockers CCBs, ACEI nor beta-blockers BBs are more effective than thiazide diuretics TZDs in reducing mortality or the incidence of stroke. The efficacy of the TZD chlorthalidone is supported by the highest-level evidence, three comparative clinical trials versus placebo, an ACEI, or a CCB, in more than 50 000 patients. In one of these trials, chlorthalidone was superior to the ACEI lisinoprilin preventing stroke; and to the CCB amlodipine in preventing heart failure. The effect of hydrochlorothiazide HCTZ , combined with amiloride or triamterene, on cardiovascular morbidity and mortality has been demonstrated in three comparative clinical trials versus placebo, BBs, or a CCB. HCTZ appeared more effective than the BB atenolol in reducing the incidence of coronary events. Indapamide another TZD is less convincing that it is more effective than chlortalidone or HCTZ. None of the antihypertensive drugs appears to have a better overall adverse effect profile than the others. Thiazide diuretics can provoke hyperglycaemia and diabetes, although this does not reduce their efficacy in the prevention of cardiovascular events. As in 2004, in 2014, the first-choice treatment for hypertension in nondiabetic adults without cardiovascular or renal disease should be a thiazide, possibly combined with amiloride or triamterene. When a diuretic cannot be used, it is better to choose an ACEI: captopril, lisinopril or ramipril.

But TZDiuretic halflife is at best 15hrs (HCTZ); and for smoother hypertension control they need to be gentle and not major diuresis-inducing, so that they do not disturb sleep or daytime function. and TZDs dont damp down compensatory heart speedup and arrhythmia, or lipidemia-hyperglycemia- which reserpine does. and lowdose reserpine doesnt cause the cough or breathlessness that ACEI, ARBs or BBs may.

This review needs to be read with Shamon & Perez‘ 2009 University of British Columbia Canadian Cochrane report : the first systematic review of reserpine for essential hypertension: “Many antihypertensive agents exist today for primary hypertension (systolic blood pressure >/=140 mmHg and/or diastolic blood pressure >/=90 mmHg). Reserpine was a second-line therapy in some of those trials. Included studies were truly randomised controlled trials comparing reserpine monotherapy to placebo or no treatment in patients with hypertension. MAIN RESULTS: Four RCTs (N =237) were found that met the inclusion criteria. The overall pooled effect demonstrates a statistically significant systolic blood pressure (SBP) reduction on reserpine compared to placebo (WMD –8mm, 95% CI -14.05, -1.78). None of the included trials reported withdrawals due to adverse effects. AUTHORS’ CONCLUSIONS: Reserpine is effective in reducing SBP roughly to the same degree as other first-line antihypertensive drugs. But this analysis is outdated because it has long been common cause that the best firstline treatment of hypertension is the balanced combination of reserpine with a potassium-sparing diuretic.

Hence combining lowdose eg 0.125mg/d or less reserpine – even 3 days a week ie 0.05mg/d- with amilozide 13-27mg/d as a morning or midday dose is ideal- especially when nighttime systolic hypertensionNSBP is the strongest predictor of CVEs cardiovascular events, as shown in a new international study in Europe, Brazil, and Japan by Universities of USA, UK and Europe: Roush, Zamalloa ea The ABC-H Investigators ; Journal of Hypertension (Oct 2014) Prognostic impact from clinic, daytime, and night-time systolic blood pressure NSBP in nine cohorts of 13 844 patients with hypertension;To determine which SBP measure best predicts cardiovascular events (CVEs- coronary artery disease CAD and stroke) independently, systematic review was conducted for all patients with hypertension,>1+ years follow-up.. Nine cohorts (n = 13 844) were from Europe, Brazil, and Japan. Results: Overall, NSBP’s dispersion exceeded DaySBP’s dispersion by 22.6% with nonoverlapping confidence limits. Within all nine cohorts, dispersion for NSBP exceeded that for ClinicSBP and DSBP ( P = 0.004) Considered individually, increases in NSBP, DSBP, and CSBP each predicted CVEs: hazard ratios (95% confidence intervals) = 1.25 (1.22-1.29), 1.20 (1.15-1.26), and 1.11 (1.06-1.16), respectively. However, after simultaneous adjustment for all three SBPs, hazard ratios were 1.26 (1.20-1.31), 1.01 (0.94-1.08), and 1.00 (0.95-1.05), respectively. Cohorts with baseline antihypertensive treatment and cohorts with patient-specific information for night-day BP classification gave similar results. Within most cohorts, simultaneously adjusted hazard ratios were greater for NSBP than for DSBP and CSBP: In hypertensive patients, NSBP had greater dispersion than DSBP and CSBP in all cohorts. On simultaneous adjustment, compared with DSBP and CSBP,increased NSBP independently predicted higher CVEs in most cohorts, and, overall, NSBP independently predicted CVEs, whereas CSBP and DSBP lost their predictive ability entirely. This trial confirms the 2012 Hosomi eaJapanese trial showing that to minimize (repeat) stroke from night BP variance, Antihypertensive medication taken in the evening or at bedtime is the most effective in treating morning hypertension when the patient adheres to the medication regimen.

There is no evidence in chronic treatment of common essential hypertension to justify loop diureticseg furosemide , as is common practice locally. .

update 12 Oct 2014For the past decade we have advocated for uncomplicated patients the gold-standard evidence-based combination of reserpine 0.0625 to 0.125 mg with 1/4 Amilozide (ie hydrochlorothiazide HCTZ 12,5mg and amiloride 1.25mg) ie HAR daily as the most cost-efficient baseline treatment of hypertension. Sometimes patients require the lower doses 1/4 tab each reserpine and Amiloretic 55mg) only 3 times a week for good control once on some cod liver oil, coconut oil and multivite-multimineral to reverse arteriosclerosis, insulin resistance, reactive oxygen species, and promote nitric oxide.

For more resistant cases we add dihydralazine 25 mg/d or amlodipine 5 to 10mg as add-ons if required – if necessary both- occasionally for optimal HBP control around 120 to 130 systolic (the new international Guideline target). With this regime of up to five drugs all more than 40 years in use, for hypertension we rarely find need to add the more costly / troublesome old eg methyldopa, or betablockers, spironolactone, or new eg ACEI or ARBs , with their cardio-respiratory risks that are so rare with the multi-low dose reserpine- amilozide- amlodipine- dihydralizane combination.

There are now 250 000 antihypertensive drug studies on Pubmed since 1947.

The latest and definitive study published on reserpine for HBP in Clin Drug Investig. 2011;31:769-77 is Long-term efficacy and tolerability of a fixed-dose combination of antihypertensive agents: an open-label surveillance study in China a massive 3 year (4500 patient-years) study by Wu Y, Li L. ea of Peking University Health Science Center, China . A fixed-dose combination (FDC) of four compounds, hydrochlorothiazide HCTZ 12.5 mg, triamterene 12.5 mg, dihydralazine 12.5 mg and reserpine 0.1 mg (HTDR), is widely used as an antihypertensive treatment in China. Although used in China for more than 30 years, there have been few comprehensive evaluations of this treatment. METHODS open-label surveillance study in Shanghai in local primary healthcare settings. Subjects with essential hypertension, aged ≥35 years at the time of enrolment. Patients with secondary hypertension, myocardial infarction or stroke within 6 months of screening, impaired renal or hepatic function, history of cardiomyopathy or chronic heart failure, or were pregnant or lactating were excluded. HTDR was administered as one or two tablets per day in the morning. If necessary, additional HCTZ was added. Blood pressure (BP) was measured every 3 months. RESULTS: A total of 1529 patients (65% female; mean age 65.7 years) entered the study with mean BP 149/89. After the 36-month treatment period, 93.1% of patients had achieved the SBP target, 97.9% had achieved the DBP target, and 92.1% had achieved both. The mean decreases in SBP and DBP were 15.3 mmHg and 9.9 mmHg, respectively. Overall, 127 adverse events in 119 patients (7.8%) occurred during the follow-up period, most of which were mild to moderate. Plasma lipids, uric acid and potassium improved. CONCLUSION: HTDR was found to have good long-term efficacy and tolerability in Chinese patients with essential hypertension.

The mean 15/10 BP lowering from a mean baseline BP of 149/89 after 3 years of the four-drug Chinese combination in China compares starkly with the mean ~51/30 mm Hg lowering (from untreated HBP of 200/120 down to ~149/90) over 4 months reported below by Alan Taylor in his 1989 thesis study in local rural Africans with similar doses of reserpine, HCTZ and dihydralazine- Taylor’s study achieving in rural Blacks in 4 months the starting BP of the Chinese some 25 years later. But the long Chinese study speaks to to the tolerance of the HTDR combination.

The China reserpine study of 1500 pts, 4500 pt years, strongly complements the ~13 trials of reserpine between 1977 (the Veterans’ Admin trial) and 1997(the German reserpine research group trials) in 7500 patients for 1 to 3 years; showing that low dose reserpine (and lowdose thiazide ) together are as good as or better than all more modern drugs- especially when augmented by amiloride.

(As Prof YK Seedat reported here in 2000), the China paper reports zero noteworthy dihydralazine risks at 12.5mg/d : J Hum Hypertens. 2000 ;14:739-47. Hypertension in developing nations in sub-Saharan Africa.Seedat YK. University of Natal, South Africa. There is a rapid development of ‘second wave epidemic’ of cardiovascular disease that is now flowing through developing countries and the former socialist republics. It is now evident from WHO data that coronary heart disease and cerebrovascular disease are increasing so rapidly that they will rank No. 1 and No. 5 respectively as causes of global burden by the year 2020. In spite of the current low prevalence of hypertensive subjects in some countries, the total number of hypertensive subjects in the developing world is high, and a cost-analysis of possible antihypertensive drug treatment indicates that developing countries cannot afford the same treatment as developed countries. Control of hypertension in the USA is only 20% (blood pressure <140/90 mm Hg). In Africa only 5-10% have a blood pressure control of hypertension of <140/90 mm Hg. There are varying responses to antihypertensive therapy in black hypertensive patients. Black patients respond well to thiazide diuretics, calcium channel blockers vasodilators like alpha-blockers, hydralazine, reserpine and poorly to beta-blockers, angiotensin-converting enzyme inhibitors and All receptor antagonists unless they are combined with a diuretic. There are social, economic, cultural factors which impair control of hypertension in developing countries. Hypertension control is ideally suited to the initial component on an integrated CVD control programme which has to be implemented. The existing health care infrastructure needs to be orientated to meet the emerging challenge of CVD, while empowering the community through health education.

Interestingly, a new metaanalysis of HCTZ trials by Musini ea Cochrane Database Syst Rev. 2014 May Blood pressure-lowering efficacy of monotherapy with thiazide diuretics for primary hypertension. shows that BP lowering over the dose range 6.25 mg, 12.5 mg, 25 mg and 50 mg/day is 4/2 mmHg, 6/3 mmHg, 8/3 mmHg and 11/5 mmHg, respectively. For other thiazide drugs, the lowest doses studied lowered blood pressure maximally and higher doses did not lower it more. Due to the greater effect on systolic than on diastolic blood pressure, thiazides lower pulse pressure by 4 mmHg to 6 mmHg. This exceeds the mean 3 mmHg pulse pressure reduction achieved by ACE inhibitors, ARBs and renin inhibitors, and the 2 mmHg pulse pressure reduction with non-selective beta-blockers as shown in other Cochrane reviews.

2009:ABSTRACT: When modern antihypertensive drugs cost far more than the old and tried, and have around 40% risk of adverse effects (Girerd 2002 Paris), and give inferior risk reduction, it is unethical for routine hypertension patients initially to be prescribed modern drugs singly or in combination in uncomplicated cases before trying the gold standard old risk-free lowdose reserpine-amilozide combination.

2009 has been a landmark year of published studies on first-line hypertension treatment.

iii. genetics and the above risk factors aside, three of the primary “endogenous” and easily correctable causes of essential hypertension are water deficiency; marine omega3 (EPA eicosapentanoic and DHA docosahexanoic acid) deficiency; and insulin resistance if not frank adiposity/overweight and diabetes.

So adequate water intake, and fish oil, and metformin/galega to tolerance, (in appropriate adipose/overweight cases) are cornerstones of antihypertensive therapy along with diet and lifestyle changes before any antihypertensive drugs are added.

Recently there have been contentious suggestion (eg Law and Ward UK 2009) that target bloodpressure should be that of youth- 120/70 down to 100/60 – as long as it does not fall so low that the patient gets dizzy on standing up. But the non-contentious gold standard remains that no one should be left with bloodpressure above at most 140/90 sitting.

ANTIHYPERTENSIVE DRUGS: There are over 34 000 RCTs, reviews and metaanalyses (since 1965) on Pubmed on these drugs.

Controlling hypertension asymptomatically before it causes damage and symptoms is the heart of successful prevention.

It is now claimed that hypertension risk starts as low as >120/70, that we should be targeting this level if tolerated.

This can only be done gently and slowly, if possible by optimising diet , lifestyle and natural supplements.

But prevention in asymptomatic patients must especially be at most a once-a-day regime, and avoid causing symptoms, and still give stable cover even if taken erratically. Only reserpine provides gentle cover lasting weeks, thus avoiding wide BP variation due to erratic dosing.

Apart from the notorious adverse effects of the older antihypertensives like guanethidine, methyldopa and atenolol, search of Pubmed under ‘ARBs, ACEI Cough;’ and under metaanalysis ‘antihypertensive cough’ with the established drugs, reveals 10 abstracts since the mid 1990s.

The nub of the matter is, the lowest-cost multiple-combination therapy (lowdose reserpine -amiloride – hydrochlorothiazide) gives the best bloodpressure and risk reduction with zero adverse effects – especially when combined with probably the best pluripotential drug of all, fish oil.. A new Cochrane metaanalysis from Univ Brit Columbia confirms that lowdose thiazide gives the best reduction of all antihypertensives in both all-morbidity and mortality outcomes -RR 0.89 (CI 0.82-0.97, p=0.0067 = highly significant) . And that metaanalysis didn’t deign to mention reserpine in the abstract.

There are at least a dozen trials each of reserpine and thiazide showing that they are the best, ideally in lowdose combination . As always, one fixed-dose combination pill (eg Brinerdin, Rautrax Imp) may work for many. But it is both cheaper, more efficient and scientific to prescribe the components separately so that reserpine and amilozide can each be titrated individually to tolerance, starting with eg reserpine (0.25mg tab ) 1/4/day and amilozide (55mg tab) 1/4 a day (costing locally retail perhaps US$0.5/month, $6/year) …

In some patients eventually this dose 3 days a week is all that is needed. With sensible advice about omitting sugar and smoking, and minimal alcohol, salt and cooked fats, and adding a multinutrient including magnesium, vitamins and the many favourable biologicals (including appropriate physiological sexhormone replacement), few patients need more than 1/2 a tab each of reserpine and amilozide for optimal BP and metabolic-vascular risk control. In the rare still- resistant cases, amlodipine is the next safest effective antihypertensive drug to add, starting with 2.5mg/d. But of course in those with insulin resistance (ie most cases), metformin is the most appropriate pluripotential drug.

Yet no trial has shown lower cost, and better superiority and safety of any modern-drug or combination over the triple-combination lowdose amilothiazide (thiazide since 1956, amiloride since 1967) with lowdose reserpine (from the ages-old rauwolfia – extracted as reserpine since 1949). Since the German Reserpine trials, and results of ALLHAT and SHEP showing that reserpine as add-on gave by far the best clinical outcomes, no head-on trials against modern drugs dare be done by drug companies or the clinicians they employ.

In 1989 pharmacist Alan Taylor published his MPharm thesis (Rhodes University) on Cost Effective Antihypertensive Therapy at A Day Hospital. – showing in a prospective randomized controlled trial for 4 months that stepped outpatient care (starting with a mean untreated BP of about 200/120) achieved the target BP ( then <165/95) in 73% compared to 11.5% on individualized treatment, and with a cost saving of 36%, with somewhat lower incidence of side effects. Hydrochlorothiazide HCT 12.5 to 25mg/d was the first step; methyldopa 250-500mg/d or reserpine 0.1mg/d as the 2nd; hydralazine 10-50mg/d low dose as the 3rd, alternatively atenolol 100mg as the 3rd or 4th step. Individualized treatment reduced bloodpressure by a mean 32.6/19 whereas stepped-care did so by 51.6/29.5mm Hg.. The HCT-Reserpine- Hydralazine-atenolol regime was the most frequently prescribed (in 61.6%),

Obviously today methyldopa, hydralazine and atenolol have become last-ditch add-ons, with amlodipine being the 1st- choice 4th drug to add to reserpine and amilozide. ,

and in 2007 Rayner, Blockman ea from the Hypertension Clinic at Groote Schuur Hospitalfound that at two community health clinics in Cape Town, only 40% of patients achieved a bloodpressure below 140/90, on a mean of 2.4 drugs per patient – clinics where reserpine and amilozide were unwisely removed from the available drug list years ago, for no plausible reason, leaving hydrochlorothiazide, atenolol, hydralazine and amlodipine as the choices- with invariably poor results in poor patients attending such free clinics.

MODERN DRUGS? But why should patients be subjected to the multiple and indisputable major risks of modern antihypertensive drugs compared to the gold standard lowdose reserpine and low dose amilozide?

From the trials and experience, lowdose amlodipine is certainly the modern drug of choice to add if counselling plus ceiling doses of reserpine and amilozide, plus fish oil plus metformin for underlying adiposity/insulin resistance, do not adequately control hypertension and other risk factors.

Why use modern drugs with their major potential hazards except for special circumstances last ditch?; when lowdose reserpine plus lowdose amilozide titrated to best effect rarely need a 4th drug added for good BP control; and practically – unlike methyldopa, guanethidine and more modern drugs- never causes persisting symptoms.

THIAZIDE ADVERSE EFFECT possible in even very low dose: anaphylaxis: Goetschalckx ea in 2007 could find exactly 49 case reports of allergic thiazide-induced pulmonary oedema in the literature after 50 years of use ie millions of patient-years. Thiazides are obviously sulphonamides, but fortunately serious- anaphylactic- reactions like lupus vascullitis and shock – are extremely rare. Wikipedia does not even mention these under thiazides, and no abstracts on Pubmed even guess at their rare incidence. 50 cases in at least 10million patient years is an incidence of below 5 per million.

We last year examined closely the trials on thiazides and reserpine 1, 2, 3.

and we published on line the only ever tabulation of all accessible trials of thiazides and reserpine, showing in the ~12 thiazide trials between 1985 (the UK MRC trial) and 2003 (the CONVINCE trial) that in 115000 patients for a mean of 4 years, thiazide is as good as or better than all more modern drugs;

and that reserpinein ~13 trials between 1977 (the Veterans’ Admin trial) and 1997(the German reserpine research group trials) in 7500 patients for 1 to 3 years is as good as or better than all more modern drugs. Of course the 2003 ALLHAT and CONVINCE papers were by far the biggest trials validating thiazide as the gold standard in 50 000 patients for 3 and 5 years respectively;

and the VA trials of 1977, 1982 and and 1990 in 1479 patients showing reserpine as equal or superior to betablockers, and the German trials of 1997 in 400 patients (Griebenow, Pittrow ea 1997) validating reserpine as equivalent to thiazide or a CCB, and the combination of thiazide and reserpine superior to an ACEI.

Now in 2009:

Shamon ea’s Cochrane review last month confirms that reserpine alone is at least equivalent in antihypertensive effect to any modern first line antihypertensive alone ;

Wald and Law’s metanalysis of single or combination antihypertensives confirms that “The extra blood pressure reduction from combining drugs from 2 different classes is approximately 5 times greater than doubling the dose of 1 drug.”

Hoffman ea’s review from New York confirms that, in autopsies of Alzheimer cases, those on antihypertensives had far less plaques that those without hypertension.

Sozen ea confirms that “ABs- Drugs with blocking effects on the renin-angiotensin-aldosterone system – do not improve endothelial dysfunction long-term in hypertensive patients”.

Mackenzie ea’sComparison of the effects of antihypertensive agents on central blood pressure and arterial stiffness in isolated systolic hypertension shows that central Pulse Pressure was only reduced significantly by perindopril, lercanidipine, and bendrofluazide, whereas atenolol had no effect. Lercanidipine reduced the augmentation index, whereas atenolol increased it. Aortic pulse wave velocity was not changed by any of the drugs. In summary, despite similar reductions in peripheral systolic and PPs with the 4 classes of drug, changes in central pressure and augmentation index varied. Because central PP and increased wave reflections are considered important risk factors in patients with isolated systolic hypertension, the choice of therapy may be influenced by these findings in the future.”

CONCLUSION: Reserpine has indisputable central and peripheral benefits in lowering central pressure via peripheral vasodilation, and via mild lowering of anxiety, cardiac rate and cardiac output; while thiazide and amiloride both lower both excessive body salt and water, while thiazide vasodilates and conserves calcium, and amiloride reverses the potassium -magnesium depletion seen in hypertension and with thiazide. .

Since the lowdose combination of reserpine and amilozide is superior to all other first-line drugs alone or in combination, and retail costs about US$1 a month in South Africa, (with negligible adverse effects compared to all other antihypertensive drugs), this combination is the mandatory firstline therapy for all hypertensive patients, with rare exceptions. This regime starts with amilozide 13.75mg (1/4 tab) and reserpine 0.0625mg (1/4tab) /d- and many patients can eventually be controlled with these doses just 3 days a week; with other antihypertensives added only if hypertension is not controlled with these increased to the ceiling tolerated eg of amilozide 27.5mg/d and reserpine 0.125 mg/d (maximum reserpine 0.25 mg 5/week ie 0.18mg/d if tolerated).

Since roleplayers are there to serve patients, not the Drug and Disease Industry, all roleplayers ( National Hypertension societies, provincial and national health and medical school authorities, medical schemes and all health practitioners) have no choice but to obey the gold-evidence-based medicine set out herein, and reinstate reserpine and amilozide as mandatory 1st-line therapy of essential hypertension, with motivation for alternatives to be provided in the exceptional cases.

Unlike the USA and the East where reserpine is still in national recommendations, Authorities, regulators, suppliers and prescribers in South Africa, Australia, the UK and Europe can no longer continue to defraud the public and deny patients this best treatment, since the two tablets (cheap amilozide and reserpine) are freely and universally available for at most the retail South African prices quoted (less in bulk buy).

There is no shortage of reserpine, HCT or amiloride; and the evidence for them over all modern antihypertensives is binding under rules of evidence and therefore medical ethics. The current evidence discussed shows that this old lowdose combination is superior to all modern drugs and modern marketted combinations in both reduction of all-cause endpoints, adverse effects, and cost.

As Henry Black said recently, triple antihypertensive therapy is simply Back to the Past – and it can be both very low cost and risk-free..

And if proof is wanted, we must agree on a simple long term multicentre trial of the lowdose reserpine-amiloretic regime versus modern marketed combinations.- as in ALLHAT but comparing combinations..But who is to pay for yet another trial to prove what is already so well proven?

35 years after Illich’s Medical Nemesis, it is very sad to have to be fighting overwhelming profiteering vested interests for what is now by far the commonest and most easily correctable major common degenerative disease – mild to moderate hypertension.

For the disabled – by arrangement drive up the ramp to the Clinic door on the Grove Bldg 1st floor parking deck.

Under CMS Council for Med Schemes Reg 10(6), open Medical schemes eg hospital plans have to pay from their own funds (not members’ savings) for appropriate outpatient consultation (tariff item 0191) for PMBs ie major conditions eg cancer, depression, neck/spinal problems, serious heart, lung, other disease., etc. Breast and osteoporosis concerns are generally part of menopause consultations N95.9 (if not already eg breast cancer code C50) and thus are often billable med scheme benefits. The menopause billable item only applies if you are 45yrs upwards, unless you have had total hysterectomy.

On patients’ requests, appropriate invoice can be prepared and submitted to your scheme for refund of your due benefits. Some schemes eg hospital plans falsely deny due benefits until reported to their regulator CMS. For medical plans where the billable tariff benefit rate is higher than the breast screening fee paid, the med plan rate 0191 will be charged eg R790 by the contracted specialist, and refundable by Discovery to the member. some basic schemes eg Keycare, Bonitas require preauthorization, or referral by their contracted GP .

Metabolic pathways are the succession of chemical changes which convert one compound into another within the body. There are many: the entire number is probably not known and there are even more subsidiary and partial pathways by which biochemical processes proceed. The pathways themselves are highly complex and depend upon routing through enzymes, co-enzymes as well accelerating and retarding factors. These routes change with different ingestants and external factors, even unlikely factors such as sunlight, in their complexity as a manufactory.

That these pathways can “learn” to take increased loads and can be trained to be more efficient and act more rapidly can be demonstrated in enhanced metabolism (“adaption”) of drugs and alcohol. Mitochondria engineer these intra-cellular modifications. This “training” might be the basis of athletic fitness (other factors such as muscle hypertrophy and muscle memory training are clearly also involved)

At simplest these pathways allow the assembly of those carbon based substances which form biological structures and allow degradation of material in order to provide energy. Disassembly of “organic” components to be reused in growth, repair, adaptation and excretion of “waste” is further role.

These biochemical pathways can be compared with complex railroad transit systems having junctions, points, lay-bys, regular sites of loading and unloading as well as the ability to regulate the load carried.

Many disease processes can be attributed to aberrations or failures of these metabolic “transport systems”. Many diseases probably occur as a result of unknown happenings in these biochemical pathways.

Therefore, if one considers nutrition, one must consider these pathways, by which ingestants are disassembled, transported through (usually) the intestinal boundaries. In themselves, these intestinal transits are highly complex, selective and prone to disease or abnormality.

21st century humans ingest in very different fashions from their evolutionary predecessors. Ingestants have changed and have become complex by a variety of manufacturing and industrial events. What then is the likelihood that the biochemical pathways have become altered, “confused” or overloaded beyond design specification? This would seem not only highly likely but to be accepted and guaranteed.

Therefore, let us look at the common ingestants, the basic feedstock of humans, and the source of their fuel-energy dynamics. Preeminent is carbohydrate. For practical purposes all carbohydrate is grown as vegetation. ( some sugars, exemplified by lactose, have animal origins) So important is food to human behaviour and existence that the wealthiest nations have, as their economic foundation, successful agriculture.

The vegetative production of carbohydrate has been substantially altered over the centuries. In broad terms, carbohydrate is not palatable and not an attractive ingestant but it has been altered to be more enticing, primarily by increasing the sugar. The fruit which we eat now has been selectively bred and is considerably sweeter than the fruit provided to primitive man (as a generalisation). Even substances like corn have been made softer, sweeter and probably fattier by selective breeding. More recently the changes of selective breeding have been accelerated by genetic engineering, but the perspective must be retained that genetic engineering has had less influence on palatability than selective breeding. Much of genetic engineering relates to enhanced production efficiency with greater yields and resistance to adverse events such as drought and disease. Shelf life has been improved and methods of removing contaminants (including contaminating infections and their by-products such as the flavo-proteins) have been forcibly and successfully addressed.

Probably the single most influential change has been the enhanced production of sugars. Not only has the feedstock been made sweeter but the sugars themselves have been produced in enormous quantities as a stand-alones or additives.

One result of the “industrialisation” of food is that carbohydrate has been changed from the highly fibrous and cellulose wrapped (and therefore relatively unpalatable). Carbohydrate is now an easily accessed and addictively attractive substance with a long shelf life, made immediately available to millions of households. Because it does not deteriorate (assisted by long-life additives) it can be snacked at will, on impulse, as a consolation or a habit from the readily available stock in most households.

Other attracting and seductive foods have been mixed with carbohydrate to make carbohydrate relatively inexpensive and highly, if not addictively, desirable. Eminent are salt and fat. Carbohydrate has been introduced into the diet of infants and children in this way and so probably changing their taste and purchase preferences forever. One has only to look at breakfast cereals where the bulk is cheap carbohydrate but “flavoured” (and for the word flavour think behaviour changing) with the two most powerful enticers, fat and sugar.

Of concern also is the industrial removal of substances from food, such as “de-bittering”. That bitterness, nature’s negative attractant is caused by a variety of substances such as tannins. These would “normally” have the effect of binding molecules and making some foods non-digestible. Removing them will increase absorbable calories, and reduce colon bulk. There is evidence that some of these lost “bitter” components could prevent cancers.

Atheroma demonstrates an analogy with gout. The “pathological substance” of atheroma is cholesterol. This is a normal constituent of the biology of humans. Cholesterol plays a vital part in the structure of the neurological system, and much more. To suggest that cholesterol can be removed from human metabolism (by reducing intake) is ludicrous. What needs to be corrected is the deposition in arterial walls. Now look at gout where the pathological substance is uric acid – a perfectly normal constituent of human metabolism. In humans uric acid is converted, by a metabolic pathway, to urea. Urea is soluble and readily excreted in urine. However if the metabolic pathway is disrupted, uric acid accumulates and disease (gout) results. This metabolic pathway disruption can be caused by genetic factors, overload by ingestion, and other physical factors. Not unlike atheroma.

The physical factor in atheroma is reflected by vascular damage by high pressures of blood, areas of blood turbulence and perhaps loss of blood vessel wall elasticity. Yet another factor might be direct damage to the arterial wall by tiny shards of metal generated in the opening of metal cans. This might explain the high incidence of atheroma in young GIs in Viet Nam: They lived on canned food, probably ingesting these metal shards which might be expected to damage arterial walls, especially in areas of is high turbulence of the blood.

Could excessive food volume alone confuse the metabolic pathways and produce disease? Could mixing different types of food taken at the same meal confuse the metabolic pathways and produce disease?

Maybe.

What about dieting? The analogy with the law of physics, “matter cannot be created or destroyed”, has lead to a dieting illusion. It is often held that losing weight can be worked on the basis “calories in = calories out (by exercise)”. Hence calorie counting. But that can be shown that is invalid as a way of reducing fat. More likely exercise (which undoubtedly can lead to loss of weight, particularly fat loss) changes the metabolic pathways (perhaps from glucose catabolism to fat catabolism), allowing selective burn of fat.

1/1/2014 again, its comforting that no new evidence of hepatotoxicity of genuine black ohosh; or kava; or (USA-grade) Herbalife products have been reported the past two years.

Teschke ea from Germany make the important point that herbaltoxicity is likely due to the “kava paradox”, that no toxicity is reported with ancient time-tested herbal remedies used appropriately by tradition in their fresh natural state and their countries of origin eg Pacifi islands; ,

but that adverse events occur with commerial eg alcohol-extracted and often preserved and old preparations, and in untested combinations with other substances especially statins, ethanol, and unknown viruses. .

The Herbalife company has just had to publish again an update rebuttalof bad papers wrongly implicating and accusing Herbalife. Their summary says:

World J Hepatol. 2013 Oct 27;5(10):601-2.. A correction of misinformation regardingHerbalife. Appelhans K, Najeeullah R, Frankos V. Herbalife International of America Inc, Torrance, CA The authors of the subject article by Senadhi et al from Indiana State University have misrepresented the safety and regulatory status of Herbalife‘s products. While we are very concerned with the unwarranted and unfavorable publicity that the inaccuracies listed could generate for Herbalife, we would welcome any inquiries that these authors may have to better clarify our commitment to the safety and quality of our products as has been demonstrated in part by our ability to establish positive relationships with regulatory authorities worldwide through continued cooperation and compliance. This letter clarifies the misinformation presented about Herbalife in the subject article

16 March 2012 it is comforting to note that there have been no new reports the past year of toxicity from these products.

In fact some lab work seems to favour black cohosh for cancer prevention;

while Herbalife has published objective rebuttals of toxicity from Herbalife other than in isolated countries where irregular ingredients were used in local manufacture:

World J Hepatol. 2011 Oct 27;3(10):275-7. Revisiting acute liver injury associated with herbalife products.Appelhans K, Smith C, Bejar E, Henig YS Herbalife International of America Inc., Torrance, CA 90502, United States. In the November 27, 2010 issue of the World Journal of Hepatology (WJH), three case reports were published which involved patients who had consumed various dietary supplements and conventional foods generally marketed as weight loss products. The reference to Herbalife products as contaminated and generally comparable to all dietary supplements or weight loss products is not scientifically supported. The authors provided an insufficient amount of information regarding patient histories, concomitant medications and other compounds, dechallenge results, and product specifications and usage. This information is necessary to fully assess the association of Herbalife products in the WJH case reports. Therefore, the article does not objectively support a causal relationship between the reported cases of liver injury and Herbalife products or ingredients.

As this colunm has previously reviewd about BC, women have died from or needed liver transplants after taking it.. Hence most Authorities have Black Box warning requirements Recurrences of liver reaction have been reported on rechallenge. These scattered cases can be argued away on metanalysis, but they cannot be ignored. One death or acute liver failure is unacceptable when BC is never an essential drug without other safe options.

Another study also published now (Wang ea from the FDA Centre for Drug Evaluation ) http://www.ncbi.nlm.nih.gov/pubmed/20920542 contradicts the German metanalysis with more basic toxicological data: “Computational analysis of positively predicted constituents showed … specifically, protocatechuic acid from black cohosh… predicted positive for liver toxicity endpoints also confirmed with literature findings”

Black cohosh is not physiological hormone replacement, BC is recommended by its proponents solely for menopause symptoms (it has no other benefits) for up to 6 months.

So why risk, use black cohosh at all?

Appropriate balanced hormone replacement – preferably human hormones, not xenohormones ie hormones not found in the healthy women, and not by swallowing it- is indicated permanently in all women .

As previouslly pointed out in this column, the International Menopause Society has summed it up in putting approriate HRT as the main agent(s) for menopause symptoms as well as for its permanent multisuystem benefits; and the human hormone gamma-aminobutyric acid GABA as the only alternative that is both safe and cleearly proven better than placebo for improving both hot flashes and sleep, anxiety. Used appropriately and with sensible monitoring and dose titration, all such hormone balance has no longterm risks.

MDICOLEGAL LIABILITY: under the new Conumae Protection Act CPA in South Africa, the pendulum has gone ridiculously too far. irrespective of the onus on manufacturers and promoters of any product, the onus is on the end-prescriber, end-dispenser to warn consumers of potential risks, and any consumer claim for consequent damages is legally against only the final and retail supplier.

So no supplier of black cohosh is protected against consequent liability unless he gets a signed waiver from the purchaser after the recorded warning about its potential toxicity.

16 June 2010

there are no new adverse toxicity reports on Hebalife, black cohosh or kava so far in 2010 .

Both Herbalife, and black cohosh products, remain marketed and in demand in South SAfrica.

There are no new serious adverse reports or concerns published on Pubmed or Google about Herbalife products in 2009.

On Pubmed there were 2 new cases of liver and coagulation problems associated with black cohosh in mid2009, from a Germanic and an Italian institute; and 14 hepatitis cases associated with kava ingestion confirmed from around the world .

4 Jan 2009

This review is not about benefit of black cohosh (independent trials show none for menopause symptoms) or Herbalife (trials support that Herbalife is indeed a weight loss aid), or kava (it is a confirmed anxiolytic analgesic euphoriant); but about toxicity potential however rare – considering that none of these products can make any claim to being a necessity.

Contamination aside, there are no new relevant reports on Herbalife the past two months on Pubmed,

but indeed 4 new reports on black cohosh; and one on kava.

Lessons for black cohosh and Herbalife may be learnt from kava. Kava-kava was hastily banned eg in Europe and South Africa early this decade owing to reputed association with hepatotoxic deaths. But on careful study these toxicity claims appear to be uncertain.

The claimed benefits of kava are analgesic, euphoriant and relaxant, without addiction potential. The four trials of Kava (between 1991 and 2003, in Italy and Germany) confirmed that kava has anxiolytic benefits in the menopause syndrome.) . The hepatotoxicity (not reported from the source – Polynesia – unless taken by alcoholics) was reported largely from western countries, where commercially sold kava extract was apparently differently extracted, and from the aerial leftovers of the kava; whereas in Polynesia it is extracted only from the root. A recent website from the NIH shows it is not banned there, but expresses much caution.

A careful analysis of kava hepatotoxicity by Teschke ea in Germany last month again finds little evidence of toxicity if kava is taken from a reputable manufacturer at prescribed dose and for short duration – as applies equally to alcohol, and most drugs.

Herbalife

An objective NICUS Nutritional Institute of University of Stellenbosch Report critical of Herbalife is quoted verbatim in the Summer 2008 Newsletter of the Association of Dieticians of SA. NICUS- a world authority in Nutrition – confirms it stands by this report. It could thus be taken as a directive (to condemn Herbalife)- to dieticians for whose professional advice some patients wrongly substitute diet supplements; where these modalities- careful professional diet advice and counselling, and supplements- are actually complementary..

But there does not appear to be any more evidence to condemn Herbalife than there was a year ago. As far as Pubmed and Google reveals, the reports [to date end of 2008 on Pubmed) of adverse effects were from 4 discrete European regions [ Iceland; Switzerland; Spain & Israel) , apparently wth locally formulated Herbalife, not the USA main factory product, leading to assumption of a local production fault. There appear to have been 2 cases of liver failure in some 33 affected patients, in one of whom liver transplant became necessary but the patient died.. .

One cannot condemn all babyfood because some is deliberately adulterated with melamine by ruthless Chinese sham factories. Commercial babyfood is arguably a necessity for many.

We await an updated rebuttal from Herbalife in the new year- but there does not seem to be anything for them to add to their rebuttal of last year..There has been no published evidence to justify update on Herbalife during 2008.

The accusation (by one patient, and a convicted fraudster, Minkow) of a claimed lead-contaminated Herbalife batch in California has, strangely, generated no updates for months now- but on the wiki herbalife update , it says “In August 2008, Minkow retracted all accusations against Herbalife and removed any mention of the company from his Web site.[30]” – there is no report of whether Herbalife bought his silence or not , which is a pity- see also. ; but see also heavy flak against Minkow , suggesting that his whole campaign was a successful bear scam to profit from Herbalife shares.

The current Wiki Herbalife review also quotes a new trial validating benefit for weightloss. Caveat Emptor.

It may be asked why a Nutritional authority like NICUS: warns against Herbalife but not against the potentially fatal black cohosh. New independent analyses are both for and against them:

ie

Black Cohosh:

Analyses of case reports from Univ Florida (Palacio 2009) and Italy (Borrelli 2008) recommend caution about black cohosh for humans in view of adverse case reports; while a German analysis (Teschke 2008) exonerates black cohosh in every single case till then.

A trial from USA (Davis 2008) found that “black cohosh significantly increased the incidence of lung metastases in tumor-bearing mice compared with mice fed the isoflavone-free control diet”.

Clearly the valid divergence of opinion comes down to complex statistics of probability.

Black cohosh has been associated with severe liver failure and transplantation in a number of women on a number of continents, for which reason the local Health Products Association, like all responsible authorities , finally agreed and issued recommendations that Black Cohosh label must be black-boxed- there is no justification for it’s sale as a useful product, unlike the role than can be argued for food substitute powders.

This review is not about benefit, but safety. Regulators remain silent about drastically curtailing sale of the most lethal substances in widespread unregulated (and unnecessary) use- paracetamol, other nonsteroidal anti-inflammatories, statins for uncomplicated mild-to-moderate lipidemia, alcohol, tobacco and sugar, and pollution of everything by industrial adulteration with synthetic (often estrogenic) endocrine disruptors and virtually all fast foods with cornstarch and/or sugar.

The hysterical approval of diethylstilbestrol DES by the FDA by 1950, and for a massive 1950 maternity trial against all evidence (even though it’s toxicity was recognized by 1953, it’s sale anywhaere was finally banned only 20 years later) continues to torment the original myriads of guineapig women, their children and now grandchildren. These scandals are dictated by individual opportunist, corporate and governmental greed, and indifference to medical evidence and prevention.

The analogy for black cohosh, kava and Herbalife is perhaps:

#the ~20year delays before the FDA would licence the lifesaving lithium salt, and metformin, in USA;

#the ~5year hysteria over HRT after the Women’s Health Initiative – when the over-estimated risks of inapproriate use of OHT in elderly women were stupidly and harmfully (for thousands of women) extrapolated to young women and other HRT preparations;

and

#the melamine- baby milk formula catastrophe – the problem for the latter was exclusively some contaminated babyfood batches made in China especially for the lucrative export market. .

The jury can thus be considered as still out on both black cohosh, kava and Herbalife, until manufacturers of commercial products (not traditional preparations of eg kava and black cohosh taken by residents who grow these) can produce evidence, confirm that the risk was limited to specific batches of the commercial product and adherence to accepted recommendations, and not due to other possible risk factors.

LIVER DAMAGE IN EUROPE ASSOCIATED WITH HERBALIFE USE:

4 Sept 2007 Review
The following reports below of HerbaLife-associated liver failure appear on Medline – from Spain, then Israel and Switzerland.
:The July 2007 reports of the two dozen Herbalife-associated hepatitis cases from Israel & Switzerland reveal that liver problems occurred after about 5 months on the products; and that relapse occurred in about 20% on rechallenge with Herbalife ie in this percentage the association is proven.

Herbalife results for weight control have been reported as good. The only problem is historical according to the current Wikipedia entry: “Some of the original Herbalife weight loss products contained the active ingredient Ma Huang or Sida cordifolia, two herbs containing ephedrine alkaloids.

Adverse reactions involving the company’s Thermojetics original green tablets were recorded by the U.S. Food and Drug Administration and Herbalife subsequently stopped using ephedrine in its products in the face of rising insurance premiums.[3][4] The U.S. FDA banned supplements containing ephedra in 2004.[5]“

It is possible that the case reports below are unrelated to Herbalife itself , or that in those countries ephedra-containing Herbalife was still in use at the time, or that potentially hazardous herbs etc were added locally.

A score of drugs and herbs can cause liver damage, topical ones – albeit rarely- include mushrooms; black cohosh and kava – see a recent list.

Drugs like ticrynafen, methyldopa and cerivastatin were discarded among other reasons because of liver problems, which are among many reasons why necessary sex hormone contraception and replacement should rather not use designer patent ie synthetic drugs, and especially not by mouth (hepatic first pass effect).

So it is always difficult to blame a single product, as the ongoing debate about black cohosh shows – which many “first world” regulators have “black boxed” ie added a compulsory warning to black cohosh warnings.

As with black cohosh, with a rare adverse event report, users of such products must weigh up for themselves.

As they say, since Herbalife tends to be custom-made in each country, with numerous ingredients (some undisclosed), it is so far impossible to incriminate whether the cause was local product corruption, or some appreoved component, of which the known possible culprits are ephedra and camelia.

Other known hepatotoxic herbs like black cohosh, kava and mushrooms were not mentioned. A few of the patients had viral hepatitis. Only 7 cases had also taken other known potential liver sensitizers – some synthetic sex hormones (4), aspirin (3), statin (1) and hydrochlorothiazide(1), of which 2 cases had positive recurrence of hepatitis on rechallenge with Herbalife.

UCT Medicines Information Centre is unaware of any such problems locally, and can recollect only perhaps 2 queries about Herbalife in some 23 years. Clarification is awaited from Herbalife headquarters.

From Swiss data the estimated incidence was below 2 cases per million Herbalife users, but both studies were based only on hospital records.

Considering the severe global problem of hepatitis from other causes (due to alcohol; obesity/diabetes (steatohepatitis, sulphonylureas, glitazones); numerous infections; carbon tetrachloride; synthetic sex hormones (oral contraception and postmenopausal hormone therapy) , mushrooms, antibiotics and antivirals, , autoimmune disease, antiepileptics, nifedipine, amitryptiline, allopurinol, nonsteroidal anti-inflammatories including aspirin and paracetamol , black cohosh, kava, antifungals and paracetamol), and that the rare adverse association of herbalife with liver damage may well have been limited only to Herbalife products made in those three “European” countries at that time, there is clearly no cause for alarm about Herbalife – just awareness.

The centuries-proven plant galega officinalis (extract) metformin after 85years of modern use remains the only drug proven in longterm use to both reduce liver damage, lipidemia, thrombosis, adiposity and insulin resistance, and thus almost halve the incidence of new diabetes, hypertension/vascular disease, cancer and thus all-cause premature medical mortality.

In defence of free market enterprise and choices, those who choose convenience safe proven food substitutes or other complementary products as part of an acceptable balanced regime advocated by suppliers like Herbalife do well, they should just be sure of the ingredients and supplier; and they should report and discuss what they use with some knowledgable up-to-date healthcare provider.

ResponsefromHerbalife

04.09.07Herbalife’s South Africa CEO responds reassuringly:

Good day,
Herewith a statement from Herbalife in response to the issues raised by yourself earlier in the week:

While we are aware of reports of abnormal liver function blood tests such as those reported by Dr. Oneta, our extensive consultation with internationally recognised liver experts has led repeatedly to the conclusion that these associations in time cannot be linked to any Herbalife product.

These small numbers of reports are anecdotal and millions of satisfied customers all over the world have been using our products for more than 27 years. All Herbalife products are formulated and manufactured in accordance with strict standards overseen by the Herbalife Scientific Advisory Board, which is chaired by David Heber, M.D., Ph.D., F.A.C.P., F.A.C.N. Quality control is overseen by our Scientific Affairs Group, chaired by Y. Steve Henig PhD and made up of an international panel of experts in nutrition and botanical dietary supplements.

Herbalife products, which are now sold in 65 countries, are formulated, registered and labelled in accordance with the regulatory requirements in every market where sold. All Herbalife products are safe to consume as directed.

Many consumers who choose to use Herbalife weight-management products for weight loss are overweight, some significantly so. Pre-existing medical conditions such as obesity and diabetes can be associated with non-alcoholic fatty liver disease, a disorder that may return certain types of abnormal blood test results. These test results, therefore, may have nothing to do with any herbal supplement, but rather are the result of a pre-existing medical condition. In addition, it is possible for an individual to have an allergic reaction to our products, the same way one might to any food product; for example, strawberries or shellfish. Herbalife supports the recommendation that consumers visiting their doctors for medical treatment inform them of any supplements they may be taking.

As a socially responsible company, we operate an adverse event reporting procedure that deals with the small number of queries we have from doctors and consumers and we operate an open dialogue policy with the medical community. All adverse event reports are investigated thoroughly in consultation with the consumer and the physician (if they are available) to fully understand the facts. None have resulted in the compulsory withdrawal of any product, ever. In the United States, Herbalife actively lobbied Congress to pass legislation mandating the submission of all dietary supplement and over-the-counter drug serious adverse events to the Food & Drug Administration. That new law takes effect December 22, 2007.”

REFS:

J Hepatol. 2007 Oct;47(4):521-526. Herbal does not mean innocuous: Ten cases of severe hepatotoxicity associated with dietary supplements from Herbalife((R)) products. Schoepfer AM, ea.University Hospital Bern, Switzerland.
METHODS: To determine the prevalence and outcome of hepatotoxicity due to Herbalife((R)) products. A questionnaire was sent to all public Swiss hospitals. Reported cases were subjected to causality assessment using the CIOMS criteria. RESULTS: Twelve cases of toxic hepatitis implicating Herbalife((R)) preparations (1998-2004) were retrieved, 10 sufficiently documented to permit causality analysis. Median age of patients was 51 years (range 30-69) and latency to onset was 5 months (0.5-144). Liver biopsy (7/10) showed hepatic necrosis, marked lymphocytic/eosinophilic infiltration and cholestasis in five patients. One patient with fulminant liver failure was successfully transplanted; the explant showed giant cell hepatitis. Causality assessment of adverse drug reaction was classified as certain in two, probable in seven and possible in one case(s), respectively. CONCLUSIONS: We present a case series of toxic hepatitis implicating Herbalife((R)) products. Liver toxicity may be severe. A more detailed declaration of components and pro-active role of regulatory agencies would be desirable.

J Hepatol. 2007 Oct;47(4):514-520. Association between consumption of Herbalife((R)) nutritional supplements and acute hepatotoxicity. Elinav E, ea -Hebrew University Medical Center, Israel.
: In 2004, identification of four index cases of acute hepatitis associated with Herbalife((R)) intake led to a ministry of health investigation in all Israeli hospitals. Twelve patients with acute idiopathic liver injury in association with consumption of Herbalife((R)) products were investigated.
RESULTS: Eleven of the patients were females, aged 49.5+/-13.4 y. One patient had stage I primary biliary cirrhosis and another had hepatitis B. Acute liver injury was diagnosed after 11.9+/-11.1 months of initiation of Herbalife((R)) consumption. Liver biopsies demonstrated active hepatitis, portal inflammation rich with eosinophils, ductular reaction and parenchymal inflammation with peri-central accentuation.
. CONCLUSIONS: An association between intake of Herbalife((R)) products and acute hepatitis was identified in Israel. We call for prospective evaluation of Herbalife((R)) products for possible hepatotoxicity.

Health- slante, l’chaim!, hayah, sawubona! – in any country orlanguage is a blessing, a gift- not a right. It is insurance that has to be planned and enforced. Leaving it to fate, illness and hoping for a cure is often too late, sometimes crippling if not often fatal. With comprehensive natural supplements, we can and should all die peacefully at an active fit advanced age 90years + – not old, incapacitated and demented. We owe this prevention to both ourselves, our kids and our aging seniors.

So sensible lifestyle aside, promoting health includes simple low-cost (no-xray/no-laboratory) periodic screening: for all, from childhood: of weight, girth, eyes, teeth, bloodpressure, brainfunction- memory; and ultrasound bones – at any pharmacy/ optometrist, school or clinic; and for women: checking the breasts and pelvis for risk of cancer.

The HealthSpanLife South African Natural Medicine Clinic SANMC next to Cavendish Mall on the slopes of Table Mountain in beautiful Cape Town – one of the favourite world tourist and heritage centres- is a specialist clinic staffed by experienced registered professional practitioners- a medical internist specialist (also UK registered); a homeopath; and a Muslim nursing sister.

It provides one-stop holistic screening and diagnostics, and – uniquely- evidence-based natural remedies- nutritional support for all symptoms and chronic conditions- also for menopause-andropause-genitourinary- breast-sexual dysfunction- obesity-pain/headache –chiropractic and detox ,

as well as if needed appropriate modern specialized testing and prescription medicines for all chronic major conditions including bio-identical hormone replacement for both genders (including implants);

Gentle Non-xray ultrasound bone-density measurement (recommended by Cape Town , UK, and USA universities), and tactile mechanical breast mapping (recommended by CANSA, UK, USA, Indian and Chinese studies) are available at SANMC (and in Gauteng) by appointment, and are covered by some medical aid plans; whereas menopause consultations are covered by all open plans.

As typified by a new review last month, World opinion is to use xray mammography and xray bone density imaging only as last resort and only in the elderly – or in staging those with breast cancer- because of the major problems and risks of xray imaging.. As world experts Profs Cornelia Baines epidemiologist in Canada, Mike Baum breast surgeon in London and Peter Gotzsche epidemiologist in Denmark say, there never has been any independent scientific evidence to support hazardous routine mass mammography crush xray screening of well women, let alone any repeated mass xray screening for decades, or the dangerous fictitious marketing hype of the American radiology-Breast Surgeons and Curves International nonsense that xray mammo screening saves lives ..

While health tariffs must rise with inflation, where med aid doesn’t cover, New Year 15% discount applies through January on cash-paid clinic services and in-house products. . .

For appointments visit the SANMC at 1st floor no. 15 Grove Medical Bldg on Pearce St cnr Grove Ave (parking opposite at ABSA on Grove); or phone +2721-6831465/ -6717415; or fax +27865657215; or email the manageress, doctors or Sister at sales@healthspanlife.co.za to discuss needs, timing and preliminary costing. For details, references and rationale for screening and prevention, see https://healthspanlife.wordpress.com/?s=screening.